Search

Introduction: Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Methods: Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. Results: The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. Conclusion: The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models. [ABSTRACT FROM AUTHOR]

For the delivery of the drug, the oral route is the most preferable due to ease of administration. However, the effective delivery of poorly aqueous soluble drugs is very challenging for the pharmaceutical scientist which leads to a low drug permeation profile across the biological membrane, poor drug bioavailability, and ultimately low therapeutic profile with less patient comfort. The inclusion of a therapeutic agent into the nanostructured-based lipid carrier can improve the limitation associated with the poorly soluble drug and it includes better drug therapeutic, pharmacokinetic profile, and controlled drug release up to a longer duration of time which causes patient compliance. Nanostructure lipid carriers (NLCs) are nanosized-based carrier systems which comprise solid lipid matrix combined with liquid lipids and surfactants. The aim of the paper is to explore the various advantages of formulation technology along with the characterization parameter of the NLCs and also report the clinical finding of the investigated NLCs for oral drug delivery system. This paper also highlighted the various patents on the NLCs. [ABSTRACT FROM AUTHOR]

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol®888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly (p < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders. [ABSTRACT FROM AUTHOR]

The encapsulation of essential oils (EOs) in nanostructured lipid carriers (NLCs) represents a modern and sustainable approach within the agrochemical industry. This research evaluated the colloidal properties and insecticidal activity of NLCs loaded with thyme essential oil (TEO-NLC) and rosemary essential oil (REO-NLC) against three common arthropod pests of ornamental flowers: Frankliniella occidentalis, Myzus persicae, and Tetranychus urticae. Gas chromatography–mass spectrometry (GC-MS) analysis identified the major chemical constituents of the EOs, with TEO exhibiting a thymol chemotype and REO exhibiting an α-pinene chemotype. NLCs were prepared using various homogenization techniques, with high shear homogenization (HSH) providing the optimal particle size, size distribution, and surface electrical charge. A factorial design was employed to evaluate the effects of EO concentration, surfactant concentration, and liquid lipid/solid lipid ratio on the physicochemical properties of the nanosuspensions. The final TEO-NLC formulation had a particle size of 347.8 nm, a polydispersity index of 0.182, a zeta potential of −33.8 mV, an encapsulation efficiency of 71.9%, and a loading capacity of 1.18%. The REO-NLC formulation had a particle size of 288.1 nm, a polydispersity index of 0.188, a zeta potential of −34 mV, an encapsulation efficiency of 80.6%, and a loading capacity of 1.40%. Evaluation of contact toxicity on leaf disks showed that TEO-NLC exhibited moderate insecticidal activity against the western flower thrips and mild acaricidal activity against the two-spotted spider mite, while REO-NLC demonstrated limited effects. These findings indicate that TEO-NLCs show potential as biopesticides for controlling specific pests of ornamental flowers, and further optimization of the administration dosage could significantly enhance their effectiveness. [ABSTRACT FROM AUTHOR]

Overactive bladder (OAB) is a usual medical syndrome that affects the bladder, and Mirabegron (MBG) is preferred medicine for its control. Currently, available marketed formulations (MYRBETRIQ® granules and MYRBETRIQ® ER tablets) suffer from low bioavailability (29–35%) hampering their therapeutic effectiveness and compromising patient compliance. By creating MBG nanostructured lipid carriers (MBG-NLCs) for improved systemic availability and drug release, specifically in oral administration of OAB treatment, this study aimed to address these issues. MBG-NLCs were fabricated using a hot-melt ultrasonication technique. MBG-GMS; MBG-oleic acid interaction was assessed by in silico molecular docking. QbD relied on the concentration of Span 80 (X1) and homogenizer speed (X2) as critical material attribute (CMA) and critical process parameter (CPP) respectively, while critical quality attributes (CQA) such as particle size (Y1) and cumulative drug release at 24 h (Y2) were estimated as dependent variables. 32 factorial design was utilized to investigate the interconnection in variables that are dependent and independents. Optimized MBG-NLCs with a particle size of 194.4 ± 2.25 nm were suitable for lymphatic uptake. A PDI score of 0.275 ± 0.02 and zeta potential of -36.2 ± 0.721 mV indicated a uniform monodisperse system with stable dispersion properties. MBG-NLCs exhibited entrapment efficiency of 77.3 ± 1.17% and a sustained release in SIF of 94.75 ± 1.60% for 24 h. MBG-NLCs exhibited the Higuchi model with diffusion as a release mechanism. A pharmacokinetic study in Wistar rats exhibited a 1.67-fold higher bioavailability as compared to MBG suspension. Hence, MBG-NLCs hold promise for treating OAB by improving MBG's oral bio absorption. [ABSTRACT FROM AUTHOR]

Yang Zheng,1,2,&ast; Limei Cui,1,2,&ast; Haoran Lu,1,2,&ast; Zhen Liu,1,2 Zhaoxue Zhai,2,3 Huikang Wang,1,2 Liting Shao,1,2 Zhaoyang Lu,2,3 Xicheng Song,1,2,4 Yu Zhang1,2,4 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, People’s Republic of China; 3Second Clinical Medicine College, Binzhou Medical University, Yantai, People’s Republic of China; 4Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Zhang, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email superzhang013@163.com Xicheng Song, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email drxchsong@163.comAbstract: The intranasal (IN) route of drug delivery can effectively penetrate the blood-brain barrier and deliver drugs directly to the brain for the treatment of central nervous system (CNS) disorders via intra-neuronal or extra-neuronal pathways. This approach has several advantages, including avoidance of first-pass metabolism, high bioavailability, ease of administration, and improved patient compliance. In recent years, an increasing number of studies have been conducted using drugs encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and delivering them to the brain via the IN pathway. SLNs are the first-generation solid lipid nanocarriers, known for their excellent biocompatibility, high drug-loading capacity, and remarkable stability. NLCs, regarded as the second-generation SLNs, not only retain the advantages of SLNs but also exhibit enhanced stability, effectively preventing drug leakage during storage. In this review, we examined in vivo studies conducted between 2019 and 2024 that used SLNs and NLCs to address CNS disorders via the IN route. By using statistical methods to evaluate pharmacokinetic parameters, we found that IN delivery of SLNs and NLCs markedly enhanced drug accumulation and targeting within the brain. Additionally, pharmacodynamic evaluations indicated that this delivery method substantially improved the therapeutic effectiveness of the drugs in alleviating symptoms in rat models of CNS diseases. In addition, methods for enhancing the efficacy of nose-to-brain delivery of SLNs and NLCs are discussed, as well as advances in clinical trials regarding SLNs and NLCs.Plain Language Summary: Traditional drug administration routes for the treatment of central nervous system diseases have many limitations due to the existence of the blood-brain barrier (BBB). The intranasal drug administration route crosses the BBB through intra-neuronal pathways as well as extra-neuronal pathways and delivers drugs directly to the brain. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are a type of nanoparticles whose surface is covered by amphoteric surfactants and whose interior is filled with a lipid core. They have the advantages of good biocompatibility, strong drug loading capacity, and strong stability, and can be obtained through a variety of reliable preparation methods. Encapsulating therapeutic drugs into SLNs and NLCs for intranasal delivery can significantly increase drug delivery efficiency and enhance efficacy. In addition, there are various ways to further enhance drug delivery of SLNs and NLCs, such as using gel systems such as chitosan to encapsulate the nanoparticles, piggybacking cell-penetrating peptides onto the surface of the nanoparticles, and modifying the nanoparticles, surface charge of particles, etc. Keywords: solid lipid nanoparticle, nanostructured lipid carrier, intranasal delivery, central nervous system diseases

Abstract Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Tamer M Shehata,1,2 Bandar Aldhubiab,1 Heba S Elsewedy3 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Alhofuf, Al-Ahsa, 36362, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 11597, Saudi ArabiaCorrespondence: Heba S Elsewedy; Tamer M Shehata, Email hsewedy@um.edu.sa; tshehata@kfu.edu.saBackground: Monitoring noncommunicable diseases is regarded as a critical concern that has to be managed in order to avoid a wide variety of complications such as increasing blood lipid levels known as dyslipidemia. Statin drugs, mostly, Rosuvastatin (RSV) was investigated for its effectiveness in treating dyslipidemia. However, reaching the most efficient treatment is essential and improving the effect of RSV is crucial. Therefore, a combination therapy was a good approach for achieving significant benefit. Although RSV is hydrophobic, which would affect its absorption and bioavailability following oral administration, overcoming this obstacle was important.Purpose: To that end, the purpose of the present investigation was to incorporate RSV into certain lipid-based nanocarriers, namely, nanostructured lipid carrier (NLC) prepared with virgin coconut oil (CCO).Methods: The optimized RSV-NLC formula was selected, characterized and examined for its in vitro, kinetic, and stability profiles. Eventually, the formula was investigated for its in vivo hypolipidemic action.Results: The optimized NLC formulation showed a suitable particle size (279.3± 5.03 nm) with PDI 0.237 and displayed good entrapment efficiency (75.6± 1.9%). Regarding in vitro release, it was efficiently prolonged for 24 h providing 93.7± 1.47%. The optimized formula was established to be stable after 3 months storage at two different conditions; 4°C and 25°C. Importantly, including CCO in the development of RSV-NLC could impressively enhance lowering total cholesterol level in obese rat models, which endorse the potential synergistic action between RSV and CCO.Conclusion: The study could elucidate the impact of developing NLC using CCO for improving RSV anti-hyperlipidemic activity.Keywords: Rosuvastatin, natural compounds, coconut oil, nanostructured lipid carrier, optimization, hypolipidemic activity

Currently, a large number of people favor meals that are rich in nutraceuticals and phytochemical compounds, which help with the treatment or prevention of chronic diseases. Oral bioavailability is a crucial component of phytochemical bioefficiency, and endogenous mechanisms have a significant impact on how well nutraceuticals and phytochemicals are absorbed by the body. In addition to endogenous variables, exogenous factors that impact the bioavailability of bioactives include the food matrix, food processing, and food storage. Different delivery systems have evolved in this regard, and nanoscale delivery tools have also been created. Delivery methods that use nanostructured lipid carriers show benefits such as enhanced loading capacity, solubility, encapsulation effectiveness, storage stability, bioavailability, and half-life. They also provide safe food systems and regulated release. In this review, the outcomes of recent experimental reports are comprehensively reviewed. In addition, the food processing, storage, gut milieu circumstances, the release process from the food and nano delivery systems in the gastrointestinal tract (GIT) milieu, interactions with other GIT constituents, main delivery systems based on nanostructured lipid carriers for their encapsulation and eventually encapsulating technological barriers, food safety concerns, and regulatory issues of nutraceutical and phytochemical compounds are discussed.

BackgroundsThe aim of the current study was to develop a distinctive nanolipid formulation, namely, nanostructured lipid carrier (NLC), which would deliver an antibacterial medication such as mupirocin (MP). Additionally, cinnamon essential oil (CEO), which is reported to exhibit antibacterial activity, was utilized in the development process in an attempt to improve the influence of MP.MethodsAs a consequence, different MP–NLC formulations were developed using the central composite design (CCD) approach. One optimized formula was selected and incorporated within the pre-formulated gel matrix, providing the MP–NLC-gel formula for efficient topical application. MP–NLC-gel was assessed for its physical characteristics to check its suitability for topical application and evaluated for its in vitro drug release over 6 h. Furthermore, it studied the formulation for its stability at different conditions; 25°C ± 2°C and at 4°C ± 3°C for 6 months. Finally, the formulation was examined for its antibacterial performance against gram-positive and -negative bacteria.ResultsThe developed topical NLC-gel formulation demonstrated pH 5.8, viscosity 14,510 cP, and spreadability 58.1 mm, which were seemed to be satisfactory properties for successful topical application. The drug was released successfully for over 6 h with 52.9%. Additionally, it was stable in both storage conditions for 6 months since it displayed non-significant variations in its evaluated characteristics compared to those of fresh preparation. Ultimately, the developed gel formulation could inhibit the growth of different bacterial strains, especially gram-negative strains.ConclusionTo sum up, these findings would demonstrate the efficiency of NLC prepared with CEO and incorporating MP to be a promising antibacterial lipid nanocarrier.

Macrophages are well known for their involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses, particularly those of human cells. Isolation of tissue-resident macrophages from humans is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes and differentiation to monocyte-derived macrophages may provide a useful tool with which to further study these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the Regulatory Science Framework for Nano(bio)material-based Medical Products and Devices (REFINE) project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination, which may confound potential observations. The SOP was deployed in two partner institutions with broadly similar results. The work presented here shows the utility of this assay but highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some logistical challenges to the application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous non-human cell lines. [ABSTRACT FROM AUTHOR]

The aim of current study was to prepare and optimize the nanostructured lipid carrier (NLC) for transdermal gliclazide (GCZ) delivery. The melt emulsification followed by ultrasonication technique was utilized to prepare GCZ–loaded-NLC. The optimization of NLC was achieved by Box-Behnken design. The surfactant (Tween 20) % (X1), total lipid (glyceryl monostearate + Lauroglycol™ 90) % (X2), and sonication time (min) (X3) were chosen as independent variables, while particles size (Y1), polydispersity index (Y2), and entrapment efficiency (Y3) were selected as response. Further, the prepared NLC was estimated for in vitro drug release study, ex vivo skin permeation and confocal laser scanning microscopy (CLSM) studies. Results of present study demonstrated that the optimized GCZ loaded NLC formulation presented the particles size, polydispersity index, zeta potential, and entrapment efficiency of 120.4 nm, 0.316, −5.58 mV, and 87.32% respectively. The in vitro drug release study indicated drug release of 68.27 ± 2.98% and 45.87 ± 2.85% for GCZ-NLC and conventional GCZ dispersion respectively. The GCZ-NLC-Gel formulation exhibited transdermal drug permeation of 76.89 ± 2.52% as compared to conventional gel (45.65 ± 2.79%). The CLSM of rat skin treated with NLC gel exhibited a deeper permeation (35 μm) in comparison to the conventional gel (15 μm). In conclusion, GCZ loaded NLC was successfully optimized using Box-Behnken design that contributed many advantages over conventional formulation and thus demonstrating NLC as propitious carriers for the transdermal GCZ delivery. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitro and in vivo performance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25 nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3–4 h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30 days. Additionally, an in vitro hemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10–5 cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed through in vivo pharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer. [ABSTRACT FROM AUTHOR]

Quercetin (QE) is a flavonoid found in several fruits and vegetables such as shallot, onion, and apple with proven antioxidant and anti-inflammatory properties that protect against and treat airway inflammation induced by particulate matter. Nanostructured lipid carriers (NLCs) with various liquid lipid types were employed to deliver QE into the respiratory tract. Physical properties of NLC formulations including particle size, stability, and entrapment efficiency were compared. Particle size of B_VCO and B_OLO formulations was 308.0 ± 0.4 nm and 104.8 ± 1.5 nm, respectively. After the temperature cycling test, particle size of B_OLO increased, while B_VCO was not significantly different. Entrapment efficiency of NLC formulations was around 50%. After QE incorporation, QE_VCO (318.3±7.4 nm) had smaller particle size than OLO (364.6 ± 0.4 nm) and was more stable with no significant difference in particle size. Percentage viability in human fetal lung fibroblast cells (MRC-5) of NLC formulations was higher than 80% and comparable with 10% w/w of CRH40 solution, suggesting no toxicity. QE_VCO effectively prevented particulate matter-induced DNA damage by a reduction of 0.68 ± 0.17 times compared to the control group and showed potential for use as an alternative treatment for DNA damage protection triggered by particulate matter. [ABSTRACT FROM AUTHOR]

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood–brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the simultaneous effects of meloxicam and rifampin nanoformulations with solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) substrates on inhibiting the quorum-sensing system of Pseudomonas aeruginosa and preventing biofilm formation by this bacterium. Methods: Antimicrobial activity of rifampin and meloxicam encapsulated with SLNs and NLCs against P. aeruginosa PAO1 was assessed by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: The SLN formulation was associated with lower doses for the MIC and minimum bactericidal concentration in comparison to NLC. Moreover, our results demonstrated that both nanoformulations were able to produce 100% inhibition of the biofilm formation of P. aeruginosa PAO1. Conclusion: All these findings suggest that meloxicam and rifampin encapsulated with SLNs could be the most effective formulation against P. aeruginosa. [ABSTRACT FROM AUTHOR]

The topical use of sunscreens is recommended for avoiding the damaging effects of UV radiation. However, improvements are still needed in the existing products to enhance their photoprotection effectiveness and safety. This involves minimizing the use of chemical UV filters while providing enhanced and prolonged photoprotection. This work investigated novel sunscreen formulations and their UV protection effects by encapsulating Uvinul® A, Tinosorb® S, and Uvinul® T150 into nanostructured lipid carriers (NLCs) based on bacuri butter and raspberry seed oil. First, the impact of critical formulation and process parameters on NLCs' particle size was evaluated using a 22 Face Centered Central Composite Design. Then, formulations were evaluated in terms of critical quality factors, in vitro skin permeation, and in vitro and in vivo photoprotection activities. The developed NLCs-containing formulations exhibited appropriate size (122–135 nm), PdI (<0.3), encapsulation efficiency (>90%), and drug content (>80%), which were preserved for at least 90 days under different stability conditions. Moreover, these NLCs-based formulations had equivalent skin permeation to emulsion-based controls, and the addition of NLCs into sunscreen cream bases in the optimum proportion of 20% (w/w) resulted in enhanced UVA and UVB photoprotection levels, despite a 10% reduction in the total filters content. Altogether, these results describe the application of nanoencapsulated organic UV filters in innovative sunscreen formulations to achieve superior photoprotection and cosmeceutical properties. [ABSTRACT FROM AUTHOR]

Nanotechnology is a relatively new technology that creates a lot of possibilities for smart drug manufacturing and delivery techniques. Nanostructured lipid carrier (NLC) is a significant advantage over the other drug delivery system. NLC-employed gel (Nanogel), which is composed of hydrophilic polymer network-based nanoparticles, ranges from 10 nm to 1000 nm. Because of its great loading capacity, high stability, extended contact period, and thus extended therapeutic impact, nanogel has been used in topical administration. In this work, Itraconazole has been chosen as an API. With the use of Central Composite Design, NLC has been prepared with two variables. They are combined with solid lipid and liquid lipid, and with the aid of a surfactant and are stabilized in aqueous dispersion. The Hot homogenization technique was adopted for the preparation of the same. The mixture was homogenized for 20 minutes at a speed of 2000-8000 RPM which was afterwards sonicated. The formed NLCs were incorporated into hydrogel using Carbopol 934 P as a gel-forming agent. Particle size was measured with the help of the Dynamic light scattering (DLS) method. The results revealed that the particles' were in nano range (54nm - 488nm). Out of 39 optimized combination found through Design of Expert software, the matched prepared formulation (NF 3) was subjected to in vitro drug diffusion study, it was found that drug diffusion from that formulation steadily increased and remained constant after 5 hours. Drug diffusion was almost 89.15% in 7 hours. Following an ex vivo permeation investigation on goat skin of the same, it was seen that the permeation of Itraconazole through goat abdominal skin from the optimized product was around 51.67% in 7 hours. [ABSTRACT FROM AUTHOR]

This study investigated a nanostructured lipid carrier (NLC)-gel system containing luteolin (LUT), a potential drug delivery system for the treatment of psoriasis. LUT-NLC was prepared by solvent emulsification ultrasonication method. The particle size was 199.9 ± 2.6 nm, with the encapsulation efficiency of 99.81% and drug loading of 4.06%. X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the LUT-NLC. The NLC was dispersed in Carbomer 940 to form the NLC based gel. The rheological characteristics of LUT-NLC-gel showed an excellent shear-thinning behavior (non-Newtonian properties) and coincided with the Herschel-Bulkley model. LUT-NLC-gel (78.89 μg/cm2) exhibited better permeation properties and released over 36 hours than LUT gel (32.17 μg/cm2). The dye-labeled LUT-NLC presented intense fluorescence in the epidermis and dermis by the visualization of fluorescence and confocal microscopy, and it could accumulate in the hair follicles. The effect of LUT-NLC-gel on imiquimod-induced psoriasis mice was evaluated by psoriasis area severity index scoring, spleen index assay, histopathology, and inflammatory cytokines. These results confirmed that LUT-NLC-gel with high dose (80 mg/kg/day) remarkably reduced the level of inflammatory and proliferation factors such as TNF-α, IL-6, IL-17, and IL-23 in both skin lesions and blood. LUT-NLC-gel improved the macroscopic features. Therefore, the LUT-NLC-gel had great potential as an effective delivery system for skin diseases. [ABSTRACT FROM AUTHOR]

In the last few decades, several nanoparticles technologies of actives delivery systems have emerged in the formulation of personal care products. The purpose of this study is to formulate the nanostructured lipid carrier loaded with Ocimum gratissimum leaves extract (OGNLC) and to characterize the chemical and physical properties of the OGNLC formulation. Ultrasound‐Assisted Extraction (UAE) method are used in this study to obtain O. gratissimum extract with the determination of the TPC, while melt emulsification homogenization conjoined with ultrasonic homogenization method are used to prepare OGNLC samples. Two types of surfactants (Tween 80 and soy lecithin) are incorporated in the formulation to form OGNLC with various compositions (%) to determine the best formulation. The effect of varying compositions of surfactants in OGNLC samples on the mean particle size (MPS), polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE%) of OGNLC are characterized. The best formulation also was analyzed by FTIR spectroscopy, and the encapsulation efficiency are determined. The stability of OGNLC particle size was also assessed after 30 days of exposure under low and room temperature (4°C, 25°C). An optimal OGNLC consists of 2.0% O. gratissimum extract, 2.0% GMS, 10.0% VCO, and varying surfactant compositions of 2.0% of Tween 80, and 1.0% of soy lecithin by a mean particle size of 155.73 ± 1.53 nm, a PDI value of 0.203 ± 0.007, zeta potential of |−37.2| ± 0.95 mV, and encapsulation efficiency (%) of 95.70% ± 6.256%. The stability assessment of OGNLC showed that the obtained formulation is at least stable for more than 30 days. This study concludes that the composition of surfactants are important factors affecting the size and stability of the OGNLC. This is the first study to report on the synthesis of nanostructured lipid carrier loaded with O. gratissimum. [ABSTRACT FROM AUTHOR]

Papain, as potential therapeutic regime, can be utilized for managing specific diseased conditions. However, its application has been limited due to its natural instability; especially when exposed to an acidic environment with a pH lower than 2.8. Therefore, the purpose of this study is to develop a Papain-loaded Nanostructured Lipid Carriers (Papain-NLC) using the Box-Behnken design (BBD) to explore the influence of different variables on the response. In this study, an optimized model was formulated based on predicted responses and the actual results closely aligned with the predicted values. Scanning Electron Microscope (SEM) and Fourier-transform infrared spectroscopy (FT-IR) were used to analyze particle size, shape, entrapment efficiency, and drug release in order to learn more about the interactions between the formulation’s components. In vitro release studies were performed, revealing a slow release of papain from the lipid matrix, coupled with the gradual degradation of matrix. Mathematical release kinetics, specifically the first-order kinetics model effectively described this release behaviour. In vitro bioaccessibility of Papain-NLCs using static digestion model was done and samples were evaluated by LC-MS/MS analysis. The results demonstrated that the static digestion model improved the bioaccessibility of Papain-NLCs. To ensure the chemical stability of Papain-NLCs, a six-month stability study was conducted, assessing particle size, polydispersity index, zeta potential and entrapment efficiency. Remarkably, no significant changes were observed, indicating the formulations robustness and potential for practical applications. Safety evaluation of the Papain-NLC’s were performed using CaCo2 cell lines, employing MTT assay for cell viability and LDH assay for cell toxicity assessment.

AbstractOral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer.

The encapsulation of essential oils (EOs) in nanostructured lipid carriers (NLCs) represents a modern and sustainable approach within the agrochemical industry. This research evaluated the colloidal properties and insecticidal activity of NLCs loaded with thyme essential oil (TEO-NLC) and rosemary essential oil (REO-NLC) against three common arthropod pests of ornamental flowers: Frankliniella occidentalis, Myzus persicae, and Tetranychus urticae. Gas chromatography–mass spectrometry (GC-MS) analysis identified the major chemical constituents of the EOs, with TEO exhibiting a thymol chemotype and REO exhibiting an α-pinene chemotype. NLCs were prepared using various homogenization techniques, with high shear homogenization (HSH) providing the optimal particle size, size distribution, and surface electrical charge. A factorial design was employed to evaluate the effects of EO concentration, surfactant concentration, and liquid lipid/solid lipid ratio on the physicochemical properties of the nanosuspensions. The final TEO-NLC formulation had a particle size of 347.8 nm, a polydispersity index of 0.182, a zeta potential of −33.8 mV, an encapsulation efficiency of 71.9%, and a loading capacity of 1.18%. The REO-NLC formulation had a particle size of 288.1 nm, a polydispersity index of 0.188, a zeta potential of −34 mV, an encapsulation efficiency of 80.6%, and a loading capacity of 1.40%. Evaluation of contact toxicity on leaf disks showed that TEO-NLC exhibited moderate insecticidal activity against the western flower thrips and mild acaricidal activity against the two-spotted spider mite, while REO-NLC demonstrated limited effects. These findings indicate that TEO-NLCs show potential as biopesticides for controlling specific pests of ornamental flowers, and further optimization of the administration dosage could significantly enhance their effectiveness.

Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 μg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration. [ABSTRACT FROM AUTHOR]

The study aimed to protect patients' skin against ionizing irradiation during radiotherapy by using astaxanthin-encapsulated nanostructured lipid carriers (NLC-ATX). NLC-ATX was prepared by a combined method of hot homogenization and sonication. Cytotoxicity of NLC-ATX was evaluated by MTT colorimetric assay. The in vitro radioprotection of NLC-ATX for human fibroblast (HF) cells was investigated based on the level of ROS (reactive oxygen species), DNA damage, and cell death caused by X-irradiation. In addition, the in vivo radioprotection was evaluated based on the appearance and histological structure of the irradiated skin. NLC-ATX was successfully prepared, with a mean particle size, zeta potential, and encapsulation efficiency of 114.4 nm, −34.1 mV, and 85.67%, respectively. Compared to the control, NLC-ATX, at an optimum ATX concentration under in vitro condition, reduced the amount of generated ROS and DNA damage of 81.6% and 41.6%, respectively, after X-radiation, resulting in a significant decrease in cell death by 62.69%. Under in vivo condition, after the 9th day of X-irradiation (equivalent to an accumulated dose of 14 Gy), the dorsal skin of five out of six NLC-ATX-untreated mice exhibited grade-1 skin damage, according to CTCAE v5.0, while treatment with NLC-ATX protected 6/6 mice from acute skin damage. Moreover, on the 28th day after the first X-irradiation, the histological images illustrated that NLC-ATX at an ATX concentration of 0.25 µg/mL exhibited good recovery of the skin, with barely any difference noted in the collagen fibers and sebaceous glands compared to normal skin. NLC-ATX shows potential for application in skin protection against adverse effects of ionizing rays during radiotherapy. [ABSTRACT FROM AUTHOR]

A nanostructured lipid carrier containing combined curcumin (CUR) and resveratrol (RSV) was prepared and tested for its potential to accelerate wound healing through topical administration. Prepared nano lipid carrier (NLC) formulation had a particle size of 132.3 ± 4.54 nm, polydispersity index (PDI) of 0.478, and zeta potential of −16.6 mV. Entrapment efficiency (EE) for CUR and RSV was found to be 94.21 ± 0.28% and 84.61 ± 0.15%, respectively. Drug loading was found to be 8.560 ± 0.948% (for CUR) and 7.602 ± 0.452% (for RSV). NLC formulation was converted to NLC gel by incorporation of Carbopol 934 for enhancing its dermal applicability. Flux and permeability coefficient for CUR and RSV in NLC gel was found to be 22.087 µg/cm2/h, 11.299 µg/cm2/h, and 0.2208, 0.1129, respectively, through goat ear skin and 19.213 µg/cm2/h, 22.66 µg/cm2/h and 0.1921, 0.2266, respectively, through Strat-MTM membrane. Dermatokinetic study revealed significant enhancement in Cskin max and AUC0–12h in skin sample treated with NLC gel in comparison with plain gel. Also, NLC gel showed longer retention time which indicates prolonged drug action at targeted site thus, NLC gel may show better therapeutic efficacy than plain gel. [ABSTRACT FROM AUTHOR]

This study is a preliminary characterization of PEGylated nanostructured lipid carriers as potential drug delivery system using appropriate standard methods. DSC traces showed that PEG 4000 was the most crystalline of all the lipids and Softisan® 154 was the least crystalline due to high enthalpy (-36mW/mg) and low enthalpy (-8.9 mW/mg) respectively. It was noticeable that the endothermic peak heights of PEGylated lipid matrix became smaller compared with the original starting lipid. All demonstrated good potentials for use as nanostructured lipid carrier drug delivery system but LMA, LMB and LMC turned to be the preferred in other of better thermal activity. SEM analysis revealed evidence of coarse structure amorphous than the individual lipidic systems. By implication showed increase drug loading capacity, it follows that that PEGylated nanostructured might be employed as NLCs carriers to serve as alternative transdermal delivery systems to improve the solubility of some poorly soluble drugs. [ABSTRACT FROM AUTHOR]

Aim: The goal of this study is to optimisation and evaluation of dopamine-loaded NLC (NLCDOPA) for achieve dopamine concentrations into brain for treatment of Parkinson's disease which causes progressive neuronal death. Method: NLC-DOPA prepared by homogenisation method using solid lipids (Cholesterol and Soya lecithin), liquid lipid (Oleic acid) and surfactant (Poloxamer-188) as major excipients, optimised by central composite design using design expert-13 software. The optimised formulations were characterised by particle size, zeta potential, entrapment efficiency, SEM, TEM, FTIR, DSC, XRD, stability study and in-vitro drug release. The histopathology of rat brain tissues and goat nasal tissues were performed. The ex-vivo (permeability and nasal ciliotoxicity study) and in vivo pharmacodynamics study were also accomplished to determine its efficacy and potency of NLC. Result: The NLC-DOPA formulations were optimised in particle size and (EE)% with range from 85.53 ± 0.703 to 106.11 ± 0.822 nm and 82.17 ± 0.794 to 95.45 ± 0.891%, respectively. The optimised formulation F11 showing best goodness-fitted model kinetic, followed by Korsmeyer- Peppas equation and zero order kinetic. The SEM and TEM confirmed the spherical and smooth morphology of formulation. FTIR and DSC spectra were given compatibility of compound and XRD diffractograms confirmed the amorphous nature. An ex-vivo study was showed the high permeability coefficient (6.67*1 0-4 cm/min, which is twice, compare to pure drug) and there was no damage in nasal mucosa, confirmed by the ciliotoxicity study. In-vivo study was shown significant effects of optimised NLC-DOPA on locomotor activity, force-swimming test and neurochemical assessment using rotenone induced Parkinson's model on Albino Wistar rats. Conclusion: NLC-DOPA was prepared and optimised successfully with increased bioavailability of drug from the NLC into brain with reduce toxicity in effective treatment of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer. [ABSTRACT FROM AUTHOR]

Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>−20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 μg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns. [ABSTRACT FROM AUTHOR]

Quercetin is a bioactive flavonoid that possesses anti-inflammatory, antioxidant, and osteoarthritic properties. Nevertheless, quercetin does possess several limitations, including poor solubility, degradation in the gastrointestinal tract, and inadequate transdermal absorption. To address this issue, quercetin is incorporated into a nanostructured lipid carrier (NLC). The NLC is then enclosed in a membrane patch, which acts as a reservoir to maintain the stability of the drug content. The aim of this study was to investigate the physicochemical properties, release kinetics, and penetration of quercetin when formulated as NLC and incorporated into a membrane-type patch. Quercetin-loaded NLC was manufactured utilizing high shear homogenization using stearic acid as the solid lipid and oleic acid as the liquid lipid in various ratios such as 6:4, 7:3, and 8:2. Furthermore, the NLC was poured over the drug reservoir in a 3.8 cm diameter backing layer mold and covered with membrane solution. The physicochemical characteristics evaluated include particle size, polydispersity index, pH, viscosity, zeta potential, entrapment efficiency, thickness, humidity, flatness, drug content, homogeneity, release study and penetration. The result showed that Formula 1 had good characteristics among other formulas with a particle size of 533 ± 50 nm, PDI of 0.343 ± 0.01, viscosity of 322 ± 12 cps, pH of 5.84 ± 0.07, thickness of 0.32 ± 0.02 mm and produced the highest release and flux penetration, namely 0.6517 ± 0.02 μg/cm²/min and 0.0013 μg/cm²/min, respectively. NLC as reservoir in membrane-type patch with higher concentration of liquid lipids could increase release and flux penetration. [ABSTRACT FROM AUTHOR]

Diclofenac sodium, a Non-Steroidal Anti-Inflammatory medicine, is efficacious in treating osteoarthritis. However, it might cause adverse gastrointestinal symptoms and may lead to liver metabolic complications when used orally. Hence, the development of an efficacious treatment, specifically the diclofenac sodium patch with a membrane, is imperative. The goal of this research was to identify the optimal formulation for a membrane-type diclofenac sodium patch with Nanostructured Lipid Carrier (NLC) as a reservoir, using a solvent casting technique with HPMC 606 as the rate-controlling membrane. Diclofenac sodium patch with NLC Formula 1 was determined to be the most effective formula, as it showed good physical attributes such as drug content and drug homogeneity above 85%, spherical particles, a higher release flux of 12.246 ± 0.60 µg/cm²/min1/2 compared to Formula 2 and Formula 3, and the release kinetics in all formula followed the Higuchi model. Using the most optimal patch formula, a penetration test showed a higher flux penetration of 0.329 ± 0.01 µg/cm²/min compared to the comparison, which involved a diclofenac sodium patch with physical mixture. The research suggested that diclofenac sodium patch with NLC holds significant potential as a transdermal drug delivery system. [ABSTRACT FROM AUTHOR]

Payal Deepak,1 Praveen Kumar,2,3 Prashant Pandey,1 Dilip Kumar Arya,1 Shweta Jaiswal,1 Anand Kumar,1 Archana Bharti Sonkar,1 Daoud Ali,4 Saud Alarifi,4 Mohankumar Ramar,5 P S Rajinikanth1 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India; 2Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India; 3S.D College of Pharmacy and Vocational Studies, Muzaffarnagar, Uttar Pradesh, India; 4Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia; 5Department of Pharmacology and Toxicology, School of Pharmacy, University of Connecticut, Storrs, CT, 02903, USACorrespondence: P S Rajinikanth, Department of Pharmaceutical Sciences Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India, Email psrajinikanth222@gmail.comBackground: Antitumor research aims to efficiently target hepatocarcinoma cells (HCC) for drug delivery. Nanostructured lipid carriers (NLCs) are promising for active tumour targeting. Cell-penetrating peptides are feasible ligands for targeted cancer treatment.Methods: In this study, we optimized gefitinib-loaded NLCs (GF-NLC) for HCC treatment. The NLCs contained cholesterol, oleic acid, Pluronic F-68, and Phospholipon 90G. The NLC surface was functionalized to enhance targeting with the cRGDfK-pentapeptide, which binds to the αvβ 3 integrin receptor overexpressed on hepatocarcinoma cells.Results: GF-NLC formulation was thoroughly characterized for various parameters using differential scanning calorimetry and X-ray diffraction analysis. In-vitro and in-vivo studies on the HepG2 cell line showed cRGDfK@GF-NLC’s superiority over GF-NLC and free gefitinib. cRGDfK@GF-NLC exhibited significantly higher cytotoxicity, growth inhibition, and cellular internalization. Biodistribution studies demonstrated enhanced tumour site accumulation without organ toxicity. The findings highlight cRGDfK@GF-NLC as a highly efficient carrier for targeted drug delivery, surpassing non-functionalized NLCs. These functionalized NLCs offer promising prospects for improving hepatocarcinoma therapy outcomes by specifically targeting HCC cells.Conclusion: Based on these findings, cRGDfK@GF-NLC holds immense potential as a highly efficient carrier for targeted drug delivery of anticancer agents, surpassing the capabilities of non-functionalized NLCs. This research opens up new avenues for effective treatment strategies in hepatocarcinoma. Keywords: nanostructured lipid carrier, αvβ 3 integrin receptor, cRGDfK-pentapeptide, hepatocellular carcinoma, tumour targeting

This study is a preliminary characterization of PEGylated nanostructured lipid carriers as potential drug delivery system using appropriate standard methods. DSC traces showed that PEG 4000 was the most crystalline of all the lipids and Softisan® 154 was the least crystalline due to high enthalpy (-36mW/mg) and low enthalpy (-8.9 mW/mg) respectively. It was noticeable that the endothermic peak heights of PEGylated lipid matrix became smaller compared with the original starting lipid. All demonstrated good potentials for use as nanostructured lipid carrier drug delivery system but LMA, LMB and LMC turned to be the preferred in other of better thermal activity. SEM analysis revealed evidence of coarse structure amorphous than the individual lipidic systems. By implication showed increase drug loading capacity, it follows that that PEGylated nanostructured might be employed as NLCs carriers to serve as alternative transdermal delivery systems to improve the solubility of some poorly soluble drugs.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds. [ABSTRACT FROM AUTHOR]

The current study aims to synthesize the gelatin-coated nanostructured lipid carrier (NLC) to encapsulate sage extract and use this nanoparticle to increase the quality parameters of beef burger samples. NLCs were prepared by formulation of gelatin (as surfactant and coating biopolymer), tallow oil (as solid lipid), rosemary essential oil (as liquid lipid), sage extract (as active material or encapsulant), polyglycerol ester and Tween 80 (as low-molecular emulsifier) through the high-shear homogenization–sonication method. The effects of gelatin concentrations and the solid/liquid ratio on the particle size, polydispersity index (PDI), and encapsulation efficiency (EE%) of sage extract-loaded NLCs were quantitatively investigated and optimized using a combined D-optimal design. Design expert software suggested the optimum formulation with a gelatin concentration of 0.1 g/g suspension and solid/liquid lipid ratio of 60/40 with a particle size of 100.4 nm, PDI of 0.36, and EE% 80%. The morphology, interactions, thermal properties, and crystallinity of obtained NLC formulations were investigated by TEM, FTIR, DSC, and XRD techniques. The optimum sage extract-loaded/gelatin-coated NLC showed significantly higher antioxidant activity than free extract after 30 days of storage. It also indicated a higher inhibitory effect against E. coli and P. aeruginosa than free form in MIC and MBC tests. The optimum sage extract-loaded/gelatin-coated NLC, more than free extract, increased the oxidation stability of the treated beef burger samples during 90 days of storage at 4 and −18 °C (verified by thiobarbituric acid and peroxide values tests). Incorporation of the optimum NLC to beef burgers also effectively decreased total counts of mesophilic bacteria, psychotropic bacteria, S. aureus, coliform, E. coli, molds, and yeasts of treated beef burger samples during 0, 3, and 7 days of storage in comparison to the control sample. These results suggested that the obtained sage extract-loaded NLC can be an effective preservative to extend the shelf life of beef burgers. [ABSTRACT FROM AUTHOR]

Purpose: To investigate a novel co-delivery system using nanostructured lipid carriers (NLCs) for simultaneous administration of two potent anti-cancer drugs, combretastatin A-4 (CA-4) and docetaxel (DTX), against tumor cells and vasculature. Methods: The CA-4 and DTX co-loaded NLCs (C-D-NLC) were formulated and investigated for physical properties, stability, and drug release. Safety and efficacy of C-D-NLC were investigated on Lewis Lung Carcinoma (LLC) tumor cells in vitro and in vivo using cytotoxicity and anti-tumor assays. The pharmacokinetics of CA-4 and DTX in rats after intravenous injection of C-D-NLC were also studied to evaluate potential drug interactions. Results: The C-D-NLC was successfully prepared with a spherical shape, mean size of 130 nm, negative charge, high encapsulation efficiency and drug loading of 94.89, 88.16, 2.44, and 4.52 for DTX and CA-4, respectively. Also, C-D-NLC had a significant inhibitory effect on LLC cells, superior to a single drug or solution group. Combretastatin A4 did not affect the pharmacokinetics of DTX, but combretastatin-docetaxel nanostructured lipid carriers (C-D-NLC) reduced plasma clearance of CA-4 and DTX, prolonged half-life, mean residence time, and increased area under concentration curves (AUC) values. Furthermore, combretastatin-docetaxel nanostructured lipid carriers (C-D-NLC) inhibited the growth of LLC tumors in mice and reduced drug toxicity. Conclusion: Combretastatin-docetaxel nanostructured lipid carriers (C-D-NLC) sustain drug release and enhance tumor growth inhibition of CA-4 and DTX by targeting both tumor cells and vasculature. The co-delivery system prolongs drug circulation compared to solution administration. Thus, nanostructured lipid carriers (NLCs) with dual drug loading may be a promising strategy for clinical combination chemotherapy in future. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) is the main cause of cancer-related deaths worldwide, with a low five-year survival rate, posing a serious threat to human health. In recent years, the delivery of antitumor drugs using a nanostructured lipid carrier (NLC) has become a subject of research. This study aimed to develop an apigenin (AP)-loaded nanostructured lipid carrier (AP-NLC) by melt sonication using glyceryl monostearate (GMS), glyceryl triacetate, and poloxamer 188. The optimal prescription of AP-NLC was screened by central composite design response surface methodology (CCD-RSM) based on a single-factor experiment using encapsulation efficiency (EE%) and drug loading (DL%) as response values and then evaluated for its antitumor effects on NCI-H1299 cells. A series of characterization analyses of AP-NLC prepared according to the optimal prescription were carried out using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). Subsequent screening of the lyophilization protectants revealed that mannitol could better maintain the lyophilization effect. The in vitro hemolysis assay of this formulation indicated that it may be safe for intravenous injection. Moreover, AP-NLC presented a greater ability to inhibit the proliferation, migration, and invasion of NCI-H1299 cells compared to AP. Our results suggest that AP-NLC is a safe and effective nano-delivery vehicle that may have beneficial potential in the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS). We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (β), and IL-6 in serum with ELISA kits. The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was −15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1β, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect. Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

The oral route is one of the most preferred routes of administration because of its convenience and safety. Nanostructured lipid carriers (NLCs) are the second-generation nanosize solid lipid nanocarriers that are composed of solid lipids, liquid lipids, and surfactants. The lipid matrix of NLCs has an imperfect structure which allows more drug loading. Other advantages offered by NLCs include biocompatibility, biodegradability, and high encapsulation efficiency. They are considered potential nanocarriers in oral drug delivery and have particle size in the range of 50–300 nm. NLCs have shown improved oral bioavailability of lipophilic drugs. They also bypass first-pass metabolism and inhibit the P-glycoprotein (P-gp) efflux mechanism of drugs. This review mainly highlights the role of NLCs in the oral delivery of drugs and different barriers that have to be overcome to achieve drug delivery by oral route. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The objective of the present research work was to enhance the bioavailability of dolutegravir sodium (anti-HIV drug) by loading the drug into a nanostructured lipid carrier (NLC), fabricated into the patch, and administered through a transdermal route. For this experimental work, six solid lipids, ten liquid lipids, and nine surfactants were selected for initial screening. The hot high-shear homogenization and melt emulsification low-temperature solidification methods were used to prepare nanostructured lipid carrier formulation. A Taguchi screening method was employed to find out the most influencing factors on critical quality attributes (CQAs) followed by a Box-Behnken design was applied to find the relationship between the independent variables and dependent variables. The selected optimized NLC formulation was characterized, and fabricated into the transdermal patch, and evaluated in a rabbit model for various pharmacokinetic parameters. The optimized formulation was characterized for particle size, zeta potential and polydispersity index (PDI), X-ray diffraction study, transmission electron microscopy analysis, in vitro drug release study, and in vivo pharmacokinetic parameter analysis. The results revealed that the particle size was 151.1 nm, zeta potential − 19.3 mV, and PDI was found to be 0.292. The AUC (0-∞) value of the drug-loaded NLC patch was 8156.426 ng h/ml, whereas 3945.696 ng h/ml and 4751.556 ng h/ml for pure drug and drug-loaded NLC formulation. From the experimental results, it was concluded that the NLC-loaded patch showed better bioavailability, which is nearly twice that of the pure drug administered by oral route. Hence, a fabricated NLC patch will be an assured drug delivery system for ameliorating the bioavailability of dolutegravir. [ABSTRACT FROM AUTHOR]

Context: Tea tree oil (TTO) is an essential oil derived from Melaleuca alternifolia, with high antimicrobial and antifungal potential. Unfortunately, its topical antifungal efficacy is limited because it is volatile, thermolabile and easily oxidized. A formulation has been developed to overcome this problem by encapsulating TTO in a nanostructured lipid carrier (NLC). Aims: To determine the effect of the liquid to solid lipid ratio on the physicochemical properties and the stability of TTO-loaded NLC. Methods: Five formula of TTO-loaded NLCs were produced by high shear homogenization method and characterized according to their particle size, size distribution, polydispersity, zeta potential, thermal characteristics, X-ray diffraction, and terpinen-4-ol concentration. In addition, a stability study was conducted by observing its physical and chemical characteristics during storage in the refrigerator (4 ± 2°C) and at room temperature (27 ± 2°C) for six months. Results: The resulting TTO-loaded NLC had an average droplet size under 400 nm. The particle size increases with increasing amount of liquid lipid in the formula. There were insignificant changes in organoleptic properties, polydispersity index, zeta potential and terpinene-4-ol concentration during stability study for six months. However, the particle size slightly increased during the six months of storage. Furthermore, the NLC 3, which formulated with a 25:95 ratio liquid to solid lipid, was be chosen as the best formula, since it demonstrated the best physicochemical characteristic and stability. Conclusions: TTO-loaded NLC with good physicochemical characteristics and stability has been successfully developed. In addition, NLC 3 is considered as the best NLC formula, which exhibits characteristics and stability that meet the requirements.

Woo-Jin Jeon,1,&ast; Hong-Ki Lee,2,3,&ast; Young-Guk Na,1 Minwoo Jung,1 Su-Cheol Han,2 Jeong Ho Hwang,2 Eunhye Jung,4 Dasom Hwang,4 Jin Soo Shin,4 Cheong-Weon Cho1 1College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 34134, Republic of Korea; 2Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology (KIT), Jeongeup, Jeollabuk-do, 53212, Republic of Korea; 3Human Health Risk Assessment Center, Jeonbuk Branch, Korea Institute of Toxicology (KIT), Jeongeup, Jeollabuk-do, 53212, Republic of Korea; 4Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jin Soo Shin, Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea, Email jsshin@krict.re.kr Cheong-Weon Cho, College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea, Email chocw@cnu.ac.krIntroduction: The ongoing SARS-CoV-2 pandemic has affected public health, the economy, and society. This study reported a nanotechnology-based strategy to enhance the antiviral efficacy of the antiviral agent remdesivir (RDS).Results: We developed a nanosized spherical RDS-NLC in which the RDS was encapsulated in an amorphous form. The RDS-NLC significantly potentiated the antiviral efficacy of RDS against SARS-CoV-2 and its variants (alpha, beta, and delta). Our study revealed that NLC technology improved the antiviral effect of RDS against SARS-CoV-2 by enhancing the cellular uptake of RDS and reducing SARS-CoV-2 entry in cells. These improvements resulted in a 211% increase in the bioavailability of RDS.Conclusion: Thus, the application of NLC against SARS-CoV-2 may be a beneficial strategy to improve the antiviral effects of antiviral agents.Keywords: remdesivir, nanostructured lipid carrier, antiviral effect, SARS-CoV-2, virus entry

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood–brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

The topical use of sunscreens is recommended for avoiding the damaging effects of UV radiation. However, improvements are still needed in the existing products to enhance their photoprotection effectiveness and safety. This involves minimizing the use of chemical UV filters while providing enhanced and prolonged photoprotection. This work investigated novel sunscreen formulations and their UV protection effects by encapsulating Uvinul® A, Tinosorb® S, and Uvinul® T150 into nanostructured lipid carriers (NLCs) based on bacuri butter and raspberry seed oil. First, the impact of critical formulation and process parameters on NLCs’ particle size was evaluated using a 22 Face Centered Central Composite Design. Then, formulations were evaluated in terms of critical quality factors, in vitro skin permeation, and in vitro and in vivo photoprotection activities. The developed NLCs-containing formulations exhibited appropriate size (122–135 nm), PdI (90%), and drug content (>80%), which were preserved for at least 90 days under different stability conditions. Moreover, these NLCs-based formulations had equivalent skin permeation to emulsion-based controls, and the addition of NLCs into sunscreen cream bases in the optimum proportion of 20% (w/w) resulted in enhanced UVA and UVB photoprotection levels, despite a 10% reduction in the total filters content. Altogether, these results describe the application of nanoencapsulated organic UV filters in innovative sunscreen formulations to achieve superior photoprotection and cosmeceutical properties.

α-Mangostin (a xanthone derivative found in the pericarp of Garcinia mangostana L.) and propolis extract (which is rich in flavonoids and phenols) are known for their antioxidant properties, making them potential supplements for the treatment of oxidative stress-related conditions. However, these two potential substances have the same primary drawback, which is low solubility in water. The low water solubility of α-mangostin and propolis can be overcome by utilizing nanotechnology approaches. In this study, a propolis-based nanostructured lipid carrier (NLC) system was formulated to enhance the delivery of α-mangostin. The aim of this study was to characterize the formulation and investigate its influence on the antioxidant activity of α-mangostin. The results showed that both unloaded propolis-based NLC (NLC-P) and α-mangostin-loaded propolis-based NLC (NLC-P-α-M) had nanoscale particle sizes (72.7 ± 1.082 nm and 80.3 ± 1.015 nm, respectively), neutral surface zeta potential (ranging between +10 mV and −10 mV), and good particle size distribution (indicated by a polydispersity index of <0.3). The NLC-P-α-M exhibited good entrapment efficiency of 87.972 ± 0.246%. Dissolution testing indicated a ~13-fold increase in the solubility of α-mangostin compared to α-mangostin powder alone. The incorporation into the propolis-based NLC system correlated well with the enhanced antioxidant activity of α-mangostin (p < 0.01) compared to NLC-P and α-mangostin alone. Therefore, the modification of the delivery system by incorporating α-mangostin into the propolis-based NLC overcomes the physicochemical challenges of α-mangostin while enhancing its antioxidant effectiveness. [ABSTRACT FROM AUTHOR]