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This work aimed to compare the performance of trans-ferulic acid-encapsulated nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) for transport by Caco-2 cells. The NLC particles (diameter: 102.6 nm) composed of Compritol® 888 ATO, ethyl oleate, Cremophor® EL, and Transcutol® P were larger than the SLNs (diameter: 86.0 nm) formed without liquid lipid (ethyl oleate), and the former had a higher encapsulation efficiency for trans-ferulic acid (p < 0.05). In vitro cultured Caco-2 cell transport was used to simulate intestinal absorption, and the cellular uptake of NLCs was higher than that of SLNs (p < 0.05). Compared to SLNs, NLCs greatly enhanced trans-ferulic acid permeation through the MillicellTM membrane (p < 0.05). This work confirms that NLCs have better properties than SLNs in terms of increasing drug transport by Caco-2 cells. This helps to comprehend the approach by which NLC-mediated oral bioavailability of trans-ferulic acid is better than that mediated by SLNs, as shown in our previous report.

Background: Nintedanib (NTB) is a multiple tyrosine kinase inhibitor, been investigated for many disease conditions like idiopathic pulmonary fibrosis (IPF), systemic sclerosis interstitial lung disease (SSc-ILD) and non-small cell lung cancer (NSCLC). NTB is available as oral capsule formulation, but its ability to detect degradants formed through oxidative, photolytic and hydrolytic processes makes it difficult to quantify. In the current work, a novel reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated. Methods: The developed method is simple, precise, reproducible, stable and accurate. The inherent stability of NTB was evaluated using the proposed analytical method approach and force degradation studies were carried out. NTB was separated chromatographically on the Shimadzu C 18 column as stationary phase (250 ×4.6 mm, 5 µm) using an isocratic elution method with 0.1% v/v triethyl amine (TEA) in HPLC grade water and acetonitrile (ACN) in the ratio 35:65% v/v. The mobile phase was pumped at a constant flow rate of 1.0 ml/min, and the eluent was detected at 390 nm wavelength. Results: NTB was eluted at 6.77±0.00 min of retention time (t R) with a correlation coefficient of 0.999, the developed method was linear in the concentration range of 0.5 µg/ml to 4.5 µg/ml. The recovery rate was found to be in the range of 99.391±0.468% for 1.5 µg/ml concentration. Six replicate standards were determined to have an % RSD of 0.04. Conclusion: The formulation excipients didn’t interfere with the determination of NTB, demonstrating the specificity of the developed method. The proposed approach of the analytical method developed can be used to quantify the amount of NTB present in bulk drugs and pharmaceutical formulations.

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake.

Capsaicin and curcumin, the active components of chili and turmeric, are prone to instability when exposed to light. Therefore, this research aimed to enhance the photostability of both extracts via the use of antioxidants, natural sunscreen, and nanostructured lipid carriers (NLCs). NLCs were chosen for this this study due to their advantages in terms of stability, drug loading capacity, occlusive effect, skin penetration, and controlled release. The photostability of each extract and extracts mixed with antioxidants, including grape seed extract, tea extract, and chlorogenic acid, were determined. Chlorogenic acid can enhance the photostability of capsaicin from 6.79 h to 16.50 h, while the photostability of curcumin increased from 9.63 h to 19.25 h. In addition, the use of natural sunscreen (sunflower oil) also increased the photostability of capsaicin and curcumin. The mixed extracts were then loaded into NLCs. The particle size of the formulation was 153.73 nm with a PDI value of 0.25. It exhibited high entrapment efficiency (more than 95%). In addition, it effectively reduced the decomposition of capsaicin and curcumin. Importantly, the natural stabilizers chosen for NLC fabrication significantly improved the photostability of curcumin and capsaicin by 600% and 567% compared to the unstabilized counterparts. This improvement contributes to the sustainability and bioavailability of these compounds in both cosmeceutical and pharmaceutical products.

The objective of the present study was to develop and evaluate NLC–chitosan hydrogel beads for topical administration. The feasibility of the preparation technology was verified by investigating various formulation factors and the impact of chitosan hydrogel beads on the NLC. The encapsulation efficiency of NLC–chitosan hydrogel beads was above 95% in optimized process conditions. The physical characterization of the NLC–chitosan hydrogel beads showed that the NLC was distributed within the network of the chitosan hydrogel beads. Furthermore, the incorporation of NLC into the chitosan hydrogel beads was related to the electrostatic interaction between the surface of the NLC and chitosan, which influenced the lipid ordering degree of the NLC and contributed to the stability. The stability studies showed that the retention rate of quercetin in the NLC–chitosan hydrogel beads was 88.63 ± 2.57% after 10 months of storage under natural daylight. An in vitro permeation study showed that NLC–chitosan hydrogel beads exhibited superior ability in enhancing skin permeation by hydrophobic active ingredients compared to the NLC and significantly increased skin accumulation. These studies demonstrated that the use of NLC–chitosan hydrogel beads might be a promising strategy for the delivery of hydrophobic active ingredients in topical administration.

The objective of this study was to develop a versatile lipid core for the ‘brick-dust type of drugs’ (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs.

Parveen F, Madni A, Torchilin VP, et al. Int J Nanomedicine. 2022;17:2413–2434. We, the Editors and Publisher of International Journal of Nanomedicine, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 11 with images from other unrelated articles and with images within the same figure. Specifically, The image for Figure 11, Heart, Group-I, has been duplicated with the image for Figure 6, Heart, Test Group from Shah H, Madni A, Khan MM, et al. pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin. Pharmaceutics. 2022;14(1):129. https://doi.org/10.3390/pharmaceutics14010129. The images for Figure 11, Heart, Group-II and Group III, have been duplicated with the image for Figure 7, Heart, Group-I from Khan S, Madni A, Rahim MA, et al. Enhanced in vitro release and permeability of glibenclamide by proliposomes: Development, characterization and histopathological evaluation. Journal of Drug Delivery Science and Technology. 2021;63:102450. https://doi.org/10.1016/j.jddst.2021.102450. The images for Figure 11, Heart, Group-II and Group-III, have been duplicated. The images for Figure 11, Spleen, Group-II and Group-III, have been duplicated. The images for Figure 11, Kidney, Group-1, Group-II and Group-III, have been duplicated. When approached for an explanation, the authors were cooperative and provided some data for their study. However, the author’s explanation and the provided data was unable to sufficiently explain how the duplication of these images occurred and was unable to alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

The exponential growth of nanotechnology has focused on therapeutic pursuits, notably for brain disorders. Nanocarriers have submicron particle sizes, typically around 500 nm. Over the past few years, interest in nanostructured lipid carriers as alternative pharmaceutical delivery systems has increased on both the scientific and commercial fronts. It belongs to a more recent incarnation of lipid nanoparticulate systems with a solid matrix and superior room temperature stability. More recently, they have also been used in gene therapy, cancer treatment, and brain targeting. In this review, the uses and significance of nanostructured lipid carriers (NLC) in combating brain diseases have been thoroughly covered, with examples from several recent research papers. A summary of NLCs' present patent status has been provided to highlight their promising potential. Related patents and research reports associated with this topic are gathered and availed. The paper thoroughly summarizes NLCs and their application in different routes of administration. Drug administration directly to the brain via nose through NLCs is mainly focused. Nose-to-brain delivery has more benefits compared to the other routes. NLCs provide significant advantages such as targeted delivery, less toxicity, higher drug loading capacity due to imperfect structure, etc. However, the particle size of NLCs for intranasal drug delivery should be < 200 nm. Also, NLC is combined with a medical device to achieve the add-on benefits for delivering drugs effectively. According to the comprehensive review of literature and patents like CN110013471B, IN-MUM-2015-00667A, IN202021023420A, and AU2021104270A4, drug-loaded NLCs in nose-to-brain delivery show promising results. NLCs can increase bioavailability and reduce dosing frequency, indirectly reducing dose-related side effects. Intervening NLCs directly on the targeted site displays site specificity and many more benefits than conventional dosage forms. Thus, using NLCs in nose-to-brain drug delivery is invigorating. [ABSTRACT FROM AUTHOR]

Brain, predisposed to local and metastasized tumors, has always been the focus of oncological studies. Glioblastoma multiforme (GBM), the most common invasive primary tumor of the brain, is responsible for 4% of all cancer-related deaths worldwide. Despite novel technologies, the average survival rate is 2 years. Physiological barriers such as blood-brain barrier (BBB) prevent drug molecules penetration into brain. Most of the pharmaceuticals present in the market cannot infiltrate BBB to have their maximum efficacy and this in turn imposes a major challenge. This mini review discusses GBM and physiological and biological barriers for anticancer drug delivery, challenges for drug delivery across BBB, drug delivery strategies focusing on SLNs and NLCs and their medical applications in on-going clinical trials. Numerous nanomedicines with various characteristics have been introduced in the last decades to overcome the delivery challenge. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were introduced as oral drug delivery nanomedicines which can be encapsulated by both hydrophilic and lipophilic pharmaceutical compounds. Their biocompatibility, biodegradability, lower toxicity and side effects, enhanced bioavailability, solubility and permeability, prolonged half-life and stability and finally tissue-targeted drug delivery makes them unique among all. [ABSTRACT FROM AUTHOR]

Fungal infection associated with eye annually affects more than one ten lakh people globally. It can affect vision and sometimes causes complete blindness. Drug delivery through ocular route has always been a challenge, as in the eye numerous barriers are located in conjunctiva, cornea, iris-ciliary body and retina which prevents drug dose from reaching the site resulting into low bioavailability of drug. Treatment through conventional dosage form often possess disadvantage of low retention time of drug as they are flows out from the corneal cavity by tear flow and nasal drainage. To overcome these challenges, the need of the hour is to fabricate a novel drug delivery system that would overcome the barrier channels of eye and could results into enhanced drug absorption at its site of action. Till date numerous technologies viz. Nanoparticles, Nanostructured Lipid Carriers (NLC), Nano micelles, Microneedles, Liposomes etc have been developed. These technologies can overcome the barriers located in the eye and improve bioavailability of drugs. The present review highlights about nanostructured lipid carriers and their potential use in ocular delivery. The aim is to study nanostructured lipid carriers as nanocarriers to increase the permeability, solubility, bioavailability and retention time of active pharmaceutics agents through ocular administration. High-pressure homogenization, emulsification-solvent evaporation and micro-emulsion are some of the methods by which they can be prepared. So, it is concluded that nanostructured lipid carriers represent a potential nanocarrier for the reliable delivery of drugs to the ocular tissues with increased solubility, bioavailability and residence time. [ABSTRACT FROM AUTHOR]

Horizontal gene transfer (HGT) in food matrices has been investigated under conditions that favor gene exchange. However, the major challenge lies in determining the specific conditions pertaining to the adapted microbial pairs associated with the food matrix. HGT is primarily responsible for enhancing the microbial repertoire for the evolution and spread of antimicrobial resistance and is a major target for controlling pathogens of public health concern in food ecosystems. In this study, we investigated Salmonella Heidelberg (SH) and Escherichia coli (EC) regarding gene exchange under conditions mimicking the industrial environment, with the coproducts whey (SL) and chicken juice (CJ). The S. Heidelberg strain was characterized by antibiotic susceptibility standards and PCR to detect the blaTEM gene. A concentration of 0.39 mg/mL was determined to evaluate the anti-conjugation activity of nanostructured lipid nanocarriers (NLCs) of essential oils to mitigate β-lactam resistance gene transfer. The results showed that the addition of these coproducts promoted an increase of more than 3.5 (whey) and 2.5 (chicken juice) orders of magnitude in the conjugation process (p < 0.01), and NLCs of sage essential oil significantly reduced the conjugation frequency (CF) by 74.90, 90.6, and 124.4 times when compared to the transfers in the absence of coproducts and the presence of SL and CJ, respectively. For NLCs from olibanum essential oil, the decrease was 4.46-fold for conjugations without inhibitors and 3.12- and 11.3-fold in the presence of SL and CJ. NLCs associated with sage and olibanum essential oils effectively control the transfer of antibiotic resistance genes and are a promising alternative for use at industrial levels. [ABSTRACT FROM AUTHOR]

This work aimed to overcome the disadvantages of the oral administration of beta-caryophyllene and boost efficiency by developing a nanostructured lipid carrier for topical administration of the drug in skin disorders. The heat emulsification method was utilized to produce beta-caryophyllene-loaded nanostructured lipid carriers. The newly created formulation was examined for its particle size, entrapment efficiency, and zeta potential after being improved using the Box–Behnken Design. The chosen formulation underwent tests to determine its ex vivo skin retention, dermatokinetic, in vitro release, antioxidant, and confocal laser scanning microscopy study. The findings of the characterization of the nanostructured lipid carriers demonstrated that the particles had a spherical form and a size of 210.86 nm (0.263 polydispersity index). The entrapment efficiency was determined to be 86.74%, and the zeta potential was measured to be −26.97 mV. The in vitro release investigation showed that nanostructure lipid carriers were capable of releasing regulated amounts of beta-caryophyllene for up to 24 hrs. In comparison to the traditional gel formulation, the ex vivo investigation demonstrated a 1.94-fold increase in the skin's capacity to retain the substance. According to the findings of the study, nanostructure lipid carriers loaded with beta-caryophyllene have the potential to be investigated for use as a topical administration method in skin disorders with enhanced skin retention and effectiveness. [ABSTRACT FROM AUTHOR]

The concept of improving drug biopharmaceutical properties by proper selection of delivery system should begin with a rational choice of relevant dosage form, followed by the precise assessment of physicochemical compatibility between the drug delivery system (DDS) and the active pharmaceutical ingredient (API). Afterwards, according to laboratory availabilities, an efficient production method should be selected and, if possible, to take into account the opportunity for lab-upscale and prevailed industry research needs. Amid the vast diversity of nanostructured drug delivery carriers, lipid nanoparticles (LNs) stand out with their undeniable advantages like exceptive biocompatibility and multiplicity, and their importance as “green” derivatives for biochemical processes. Their distinctive structural properties also allow adequate protection of loaded APIs against chemical degradation in an aggressive biological environment and provide excellent resiliency in modifying drug release profiles. This review highlights different findings reported by the researchers worldwide over the years and focuses on the various production strategies and techniques for the preparation of LNs. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From this perspective, we have investigated how the chitosanization and PEGylation of NLCs affected their ability to function as a delivery system for apixaban (APX). These surface modifications could enhance the ability of NLCs to improve the bioavailability and pharmacodynamic activity of the loaded drug. In vitro and in vivo studies were carried out to examine APX-loaded NLCs, chitosan-modified NLCs, and PEGylated NLCs. The three nanoarchitectures displayed a Higuchi-diffusion release pattern in vitro, in addition to having their vesicular outline proven via electron microscopy. PEGylated and chitosanized NLCs retained good stability over 3 months, versus the nonPEGylated and nonchitosanized NLCs. Interestingly, APX-loaded chitosan-modified NLCs displayed better stability than the APX-loaded PEGylated NLCs, in terms of mean vesicle size after 90 days. On the other hand, the absorption profile of APX (AUC0-inf) in rats pretreated with APX-loaded PEGylated NLCs (108.59 µg·mL−1·h−1) was significantly higher than the AUC0-inf of APX in rats pretreated with APX-loaded chitosan-modified NLCs (93.397 µg·mL−1·h−1), and both were also significantly higher than AUC0-inf of APX-Loaded NLCs (55.435 µg·mL−1·h−1). Chitosan-coated NLCs enhanced APX anticoagulant activity with increased prothrombin time and activated partial thromboplastin time by 1.6- and 1.55-folds, respectively, compared to unmodified NLCs, and by 1.23- and 1.37-folds, respectively, compared to PEGylated NLCs. The PEGylation and chitosanization of NLCs enhanced the bioavailability and anticoagulant activity of APX over the nonmodified NLCs; this highlighted the importance of both approaches. [ABSTRACT FROM AUTHOR]

Pranoprofen (PRA)-loaded nanostructured lipid carriers (NLC) have been dispersed into blank gels composed of 1% of Carbomer 940 (PRA-NLC-Car) and 3% of Sepigel® 305 (PRA-NLC-Sep) as a novel strategy to refine the biopharmaceutical profile of PRA, for dermal administration in the treatment of skin inflammation that may be caused by possible skin abrasion. This stratagem intends to improve the joining of PRA with the skin, improving its retention and anti-inflammatory effect. Gels were evaluated for various parameters such as pH, morphology, rheology, and swelling. In vitro drug release research and ex vivo permeation through the skin were carried out on Franz diffusion cells. Additionally, in vivo assays were carried out to evaluate the anti-inflammatory effect, and tolerance studies were performed in humans by evaluating the biomechanical properties. Results showed a rheological profile common of semi-solid pharmaceutical forms for dermal application, with sustained release up to 24 h. In vivo studies using PRA-NLC-Car and PRA-NLC-Sep in Mus musculus mice and hairless rats histologically demonstrated their efficacy in an inflammatory animal model study. No signs of skin irritation or modifications of the skin's biophysical properties were identified and the gels were well tolerated. The results obtained from this investigation concluded that the developed semi-solid formulations represent a fitting drug delivery carrier for PRA's transdermal delivery, enhancing its dermal retention and suggesting that they can be utilized as an interesting and effective topical treatment for local skin inflammation caused by a possible abrasion. [ABSTRACT FROM AUTHOR]

Quinine hydrochloride (QHCl) has remained a very relevant antimalarial drug 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is to date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multidrug-resistant malaria parasites. The decline in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence, our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. QHCl nanosuspension (QHCl-NS) for intranasal administration was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon® 90H and lipids (Softisan® 154 or Compritol®) in a 1:2 ratio, while Poloxamer® 188 (P188) and Tween® 80 (T80) were used as a stabilizer and a surfactant, respectively. The QHCl-NS formulated were in the nanosize range (68.60 ± 0.86 to 300.80 ± 10.11 nm), and highly stable during storage, though zeta potential was low (≤6.95 ± 0.416). QHCl-NS achieved above 80% in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56-fold increase in the flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with Plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16%) was comparable to oral administration (52.12%). Therefore, redesigning QHCl as NS for intranasal administration has great potential to serve as a more tolerable option for the treatment of malaria in endemic areas. [ABSTRACT FROM AUTHOR]

Alzheimer-type dementia (ATD) treatments face limitations in crossing the blood–brain barrier and systemic adverse effects. Intranasal administration offers a direct route to the brain via the nasal cavity's olfactory and trigeminal pathways. However, nasal physiology can hinder drug absorption and limit bioavailability. Therefore, the physicochemical characteristics of formulations must be optimized by means of technological strategies. Among the strategies that have been explored, lipid-based nanosystems, particularly nanostructured lipid carriers, are promising in preclinical investigations with minimal toxicity and therapeutic efficacy due to their ability to overcome challenges associated with other nanocarriers. We review the studies of nanostructured lipid carriers for intranasal administration in the treatment of ATD. Currently, no drugs for intranasal administration in ATD have marketing approval, with only three candidates, insulin, rivastigmine and APH-1105, being clinically investigated. Further studies with different candidates will eventually confirm the potential of the intranasal route of administration in the treatment of ATD. [ABSTRACT FROM AUTHOR]

Many pharmaceutically active molecules are highly lipophilic, which renders their administration and adsorption in patients extremely challenging. Among the countless strategies to overcome this problem, synthetic nanocarriers have demonstrated superb efficiency as drug delivery systems, since encapsulation can effectively prevent a molecules' degradation, thus ensuring increased biodistribution. However, metallic and polymeric nanoparticles have been frequently associated with possible cytotoxic side effects. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which are prepared with physiologically inert lipids, therefore emerged as an ideal strategy to bypass toxicities issues and avoid the use of organic solvents in their formulations. Different approaches to preparation, using only moderate amounts of external energy to facilitate a homogeneous formation, have been proposed. Greener synthesis strategies have the potential to provide faster reactions, more efficient nucleation, better particle size distribution, lower polydispersities, and furnish products with higher solubility. Particularly microwave-assisted synthesis (MAS) and ultrasound-assisted synthesis (UAS) have been utilized in the manufacturing of nanocarrier systems. This narrative review addresses the chemical aspects of those synthesis strategies and their positive influence on the characteristics of SLNs and NLCs. Furthermore, we discuss the limitations and future challenges for the manufacturing processes of both types of nanoparticles. [ABSTRACT FROM AUTHOR]

The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently decreasing the chance of disease development. In the present study, a topical xanthan gum nanogel containing gamma-oryzanol-loaded nanostructured lipid carriers (NLCs) and nanosized UV filters TiO2 and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was developed to assess their synergistic potential in having multifunctional skin beneficial properties. The developed NLCs contained the natural-based solid lipids shea butter and beeswax, liquid lipid carrot seed oil, and the potent antioxidant gamma-oryzanol, with an optimum particle size for topical application (<150 nm), good homogeneity (PDI = 0.216), high zeta potential (−34.9 mV), suitable pH value (6), good physical stability, high encapsulation efficiency (90%), and controlled release. The final formulation, a nanogel containing the developed NLCs and the nano UV filters, showed high long-term storage stability and high photoprotection ability (SPF = 34) and resulted in no skin irritation or sensitization (rat model). Hence, the developed formulation showed good skin protection and compatibility, demonstrating promise as a new platform for the future generation of natural-based cosmeceuticals. [ABSTRACT FROM AUTHOR]

Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions. [ABSTRACT FROM AUTHOR]

This study aimed to develop a semisolid vehicle for topical delivery of nanoencapsulated St. John's wort (SJW) extract, rich in hyperforin (HP), and explore its wound-healing potential. Four nanostructured lipid carriers (NLCs) were obtained: blank and HP-rich SJW extract-loaded (HP-NLC). They comprised glyceryl behenate (GB) as a solid lipid, almond oil (AO), or borage oil (BO) representing the liquid lipid, along with polyoxyethylene (20) sorbitan monooleate (PSMO) and sorbitan monooleate (SMO) as surfactants. The dispersions demonstrated anisometric nanoscale particles with acceptable size distribution and disrupted crystalline structure, providing entrapment capacity higher than 70%. The carrier exhibiting preferable characteristics (HP-NLC2) was gelled with Poloxamer 407 (PM407) to serve as the hydrophilic phase of a bigel, to which the combination of BO and sorbitan monostearate (SMS) organogel was added. The eight prepared bigels with different proportions (blank and nanodispersion-loaded) were characterized rheologically and texturally to investigate the impact of the hydrogel-to-oleogel ratio. The therapeutic potential of the superior formulation (HP-NLC-BG2) was evaluated in vivo on Wistar male rats through the tensile strength test on a primary-closed incised wound. Compared with a commercial herbal semisolid and a control group, the highest tear resistance (7.764 ± 0.13 N) was achieved by HP-NLC-BG2, proving its outstanding wound-healing effect. [ABSTRACT FROM AUTHOR]

Ticagrelor (TCG), an antiplatelet agent, has low solubility and permeability; thus, there are many trials to apply the pharmaceutical technology for the enhancement of TCG solubility and permeability. Herein, we have developed the TCG high-loaded nanostructured lipid carrier (HL-NLC) and solidified the HL-NLC to develop the oral tablet. The HL-NLC was successfully fabricated and optimized with a particle size of 164.5 nm, a PDI of 0.199, an encapsulation efficiency of 98.5%, and a drug loading of 16.4%. For the solidification of HL-NLC (S-HL-NLC), the adsorbent was determined based on the physical properties of the S-HL-NLC, such as bulk density, tap density, angle of repose, Hausner ratio, Carr's index, and drug content. Florite R was chosen because of its excellent adsorption capacity, excellent physical properties, and solubility of the powder after manufacturing. Using an S-HL-NLC, the S-HL-NLC tablet with HPMC 4 K was prepared, which is showed a released extent of more than 90% at 24 h. Thus, we have developed the sustained release tablet containing the TCG-loaded HL-NLC. Moreover, the formulations have exhibited no cytotoxicity against Caco-2 cells and improved the cellular uptake of TCG. In pharmacokinetic study, compared with raw TCG, the bioavailability of HL-NLC and S-HL-NLC was increased by 293% and 323%, respectively. In conclusion, we successfully developed the TCG high-loaded NLC tablet, that exhibited a sustained release profile and enhanced oral bioavailability. [ABSTRACT FROM AUTHOR]

Nanostructured Lipid Carriers (NLC) are lipid-based carrier that uses a combination of liquid and solid lipids which is believed to deliver a higher amount of active substance to the human body. This study aimed to obtain the best formulation and evaluate the stability of curcumin-loaded NLC (C-NLC) using microfluidic technique at temperature of 40o C and 60o C with the ratios of liquid:solid lipids were 2: 1; 3.5: 1; 4: 1; 6: 1% w/w. Our results showed that the increase of process temperature and liquid lipid concentration reduced particle size. There was a non-linear relationship between lipid ratio and temperature to encapsulation percentage. At ratio of soybean oil:stearic acid 6: 1 and, at 40°C, particles size (PS) obtained was 143.87 ± 3.36 nm, polydispersity index (PDI) obtained was 0.44 ± 0.01, zeta potential (ZP) obtained was -33.3 ± 6.53 mV with encapsulation percentage of 20.62%. At the same ratio at 60°C, the PS obtained was 60.21 ± 2.55 nm, PDI obtained was 0.72 ± 0.03, ZP obtained was -26.10 ± 1.83 mV and encapsulation percentage of 31.45%. Stability test showed that C-NLC produced at 60°C was more stable since the change of particle size and pH were lower than C-NLC produced at 40°C. [ABSTRACT FROM AUTHOR]

In order to improve the delivery of topical corticosteroids into inflammatory skin lesions while reducing the likelihood of adverse effects, lipid nanocarriers have received increasing attention. Hence, this study aimed to develop biocompatible nanoemulsions (NEs) and nanostructured lipid carriers (NLCs) as carriers for fluocinolone acetonide (FA) by carefully optimizing the formulation and process parameters. After an analysis of the relevant physicochemical parameters and stability testing, in vitro release and permeation tests were performed to evaluate whether the nanocarriers affected the penetration of FA into/through the skin compared to a conventional reference product (Sinoderm® cream). The developed NEs exhibited satisfactory physicochemical properties (droplet size |-30| mV, pH ~ 4.75) and long-term stability. Although the developed NLCs initially had satisfactory properties, gelation was observed within 3 months of storage, implying that further formulation testing is required to resolve the limited stability of these systems. In vitro release/permeation findings suggest that the developed nanocarriers (especially NEs) provide better delivery of FA into/though the skin compared to the Sinoderm® cream. Therefore, a lecithin-based NE with a 10% lipid phase (medium-chain triglycerides/oleic acid 3:1) is a promising strategy for improved delivery of FA to the inflamed skin, allowing for ease of application, especially to larger skin surfaces and hairy regions.

Min Du,1 Jianbo Yin2 1Department of Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214000, People’s Republic of China; 2Department of Pharmacy, Wuxi Dashan Medical Beauty Clinic, Wuxi, Jiangsu Province, 214001, People’s Republic of ChinaCorrespondence: Jianbo Yin, Email yinjianbodmbc@outlook.comPurpose: Cisplatin (CDDP) and etoposide (Etp) are recommended first-line therapy for lung cancer. Nanostructured lipid carriers (NLCs) are engineered to deliver drugs for lung cancer treatment. In the present study, NLCs were applied to coload an Etp prodrug (EtpP) and CDDP.Methods: The Etp prodrug was synthesized by linking the phenolic hydroxyl group of Etp with polyethylene glycol (PEG). EtpP and CDDP coencapsulated NLCs (EtpP–CDDP NLCs) were prepared using film ultrasound. Cytotoxicity of drugs and drug-containing NLCs was assessed by evaluating cell viability using MTT assays. In vivo antitumor efficiency of EtpP–CDDP NLCs was evaluated on lung cancer–bearing xenografts.Results: EtpP–CDDP NLCs showed a uniformly spherical morphology with a size of 176.8± 4.9 nm and -potential of – 31.9± 3.2 mV. Cellular uptake efficiency of EtpP–CDDP NLCs was 57.4%± 3.9% on A549/DDP cells. EtpP–CDDP NLCs exhibited more sustained plasma retention, the highest drug distribution in tumors, and the highest tumor-inhibition rates in lung tumor–bearing mice.Conclusion: EtpP–CDDP NLCs improved tumor-cell uptake, cytotoxicity, and tumor-inhibition efficiency, and could be used as a promising drug-delivery system for lung cancer combination therapy.Keywords: lung cancer, prodrug, etoposide, cisplatin, nanostructured lipid carriers

Combination therapy combining two drugs in one modified drug delivery system is used to achieve synergistic analgesic effect, and bring effective control of pain management, especially postoperative pain management. In the present study, a combination of drug delivery technologies was utilized. Transcriptional transactivator (TAT) peptide modified, transdermal nanocarriers were designed to co-deliver ropivacaine (RVC) and meloxicam (MLX) and anticipated to achieve longer analgesic effect and lower side effect. TAT modified nanostructured lipid carriers (TAT-NLCs) were used to co-deliver RVC and MLX. RVC and MLX co-loaded TAT-NLCs (TAT-NLCs-RVC/MLX) were evaluated through in vitro skin permeation and in vivo treatment studies. NLCs-RVC/MLX showed uniform and spherical morphology, with a size of 133.4 ± 4.6 nm and a zeta potential of 20.6 ± 1.8 mV. The results illustrated the anesthetic pain relief ability of the present constructed system was significantly improved by the TAT modification through the enhanced skin permeation efficiency and the co-delivery of MLX along with RVC that improved pain management by reducing inflammation at the injured area. This study provides an efficient and facile method for preparing TAT-NLCs-RVC/MLX as a promising system to achieve synergistic analgesic effect.

Hydroxy-α-sanshool (HAS), extracted from Zanthoxylum piperitum, is commonly used in oral surgery to relief pain. However, the application of HAS is limited in clinical practice due to its poor stability. This study focuses on the design of a novel nano-formulation delivery system for HAS to improve its stability and local anesthetic effect. Hydroxy-α-sanshool loaded nanostructured lipid carriers (HAS-NLCs) were prepared by melting emulsification and ultra-sonication using monostearate (GMS) and oleic acid (OA) as lipid carriers, and poloxamer-188 (F68) as a stabilizer. Besides, the formulation was optimized by response surface methodology (RSM). Then, the best formulation was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), drug loading (DL%), differential scanning calorimetry (DSC), and morphology (transmission electron microscopy, TEM). The obtained HAS-NLCs were homogeneous, near spherical particles with high DL% capacity. The stability of HAS-NLCs against oxygen, light, and heat was greatly improved over 10.79 times, 3.25 times, and 2.09 times, respectively, compared to free HAS. In addition, HAS-NLCs could exhibit sustained release in 24 h following a double-phase kinetics model in vitro release study. Finally, HAS-NLCs had excellent anesthetic effect at low dose in formalin test compared with free HAS and lidocaine, which indicated HAS-NLCs were a potential local anesthesia formulation in practice.

Sorafenib (SRB), a multikinase inhibitor, is effective in reducing experimental corneal neovascularization (CNV) after oral administration; however, its therapeutic use in ocular surface disorders is restricted due to poor solubility and limited bioavailability. This study aimed to develop and optimize SRB-loaded nanostructured lipid carriers (SRB-NLCs) for topical ocular delivery by a central composite design response surface methodology (CCD-RSM). It was spherical and uniform in morphology with an average particle size of 111.87 ± 0.93 nm and a narrow size distribution. The in vitro drug release from the released SRB-NLC formulation was well fitted to Korsmeyer Peppas release kinetics. The cell counting kit-8 (CCK-8) cell viability assay demonstrated that SRB-NLC was not obviously cytotoxic to human corneal epithelial cells (HCECs). An in vivo ocular irritation test showed that SRB-NLC was well tolerated by rabbit eyes. Ocular pharmacokinetics revealed 6.79-fold and 1.24-fold increase in the area under concentration-time curves (AUC0-12h) over 12 h in rabbit cornea and conjunctiva, respectively, treated with one dose of SRB-NLC compared with those treated with SRB suspension. Moreover, SRB-NLC (0.05% SRB) and dexamethasone (0.025%) similarly suppressed corneal neovascularization in mice. In conclusion, the optimized SRB-NLC formulation demonstrated excellent physicochemical properties and good tolerance, sustained release, and enhanced ocular bioavailability. It is safe and potentially effective for the treatment of corneal neovascularization.

Entacapone, a reversible catechol-o-methyl transferase inhibitor, is used to enhance the action of dopamine agonists by reducing their metabolism and the ‘Wearing-off’ effects associated with long-term use in the treatment of Parkinson's disease. It is used as an adjunct to levodopa/Carbidopa therapy. Due to limited dissolution and first-pass clearance, it suffers low and variable bioavailability issues. To overcome this problem, the present study aims to explore the potential of nanostructured lipid carriers (NLCs) for the delivery of Entacapone. The Quality by Design (QbD) approach was used for the systematic development of NLCs. The 23 full factorial designs were investigated using Design-Expert®11 software. The three independent variables namely content of total lipid (X1), surfactant (X2), and sonication time (X3) were optimized against two responses namely particle size and entrapment efficiency. The optimized NLCs were characterized for their size, surface morphology, entrapment efficiency, drug release, thermal and crystallographic studies. In-vivo pharmacokinetic studies in Entacapone-loaded NLCs showed an increase in t1/2, AUC0–∞, MRT compared to free drug. The reduction in elimination (Kel) depicts the prolonged action of Entacapone by loading in NLCs. The results displayed Entacapone-loaded NLCs have promising potential for oral delivery and enhanced therapeutic effect which otherwise was a major issue.

Loratadine (LORA), is a topical antihistamine utilized in the treatment of ocular symptoms of COVID-19. The study aimed to develop a Loratadine Nanostructured Lipid Carriers Ocugel (LORA-NLCs Ocugel), enhance its solubility, trans-corneal penetrability, and bioavailability. full-factorial design was established with 24 trials to investigate the impact of several variables upon NLCs properties. LORA-NLCs were fabricated by using hot melt emulsification combined with high-speed stirring and ultrasonication methods. All obtained formulae were assessed in terms of percent of entrapment efficiency (EE%), size of the particle (PS), zeta potential (ZP), as well as in-vitro release. Via using Design Expert® software the optimum formula was selected, characterized using FTIR, Raman spectroscopy, and stability studies. Gel-based of optimized LORA-NLCs was prepared using 4% HPMC k100m which was further evaluated in terms of physicochemical properties, Ex-vivo, and In-vivo studies. The optimized LORA-NLCs, comprising Compritol 888 ATO®, Labrasol®, and Span® 60 showed EE% of 95.78 ± 0.67%, PS of 156.11 ± 0.54 nm, ZP of −40.10 ± 0.55 Mv, and Qh6% of 99.67 ± 1.09%, respectively. Additionally, it illustrated a spherical morphology and compatibility of LORA with other excipients. Consequently, gel-based on optimized LORA-NLCs showed pH (7.11 ± 0.52), drug content (98.62%± 1.31%), viscosity 2736 cp, and Q12% (90.49 ± 1.32%). LORA-NLCs and LORA-NLCs Ocugel exhibited higher ex-vivo trans-corneal penetrability compared with the aqueous drug dispersion. Confocal laser scanning showed valuable penetration of fluoro-labeled optimized formula and LORA-NLCs Ocugel through corneal. The optimized formula was subjected to an ocular irritation test (Draize Test) that showed the absence of any signs of inflammation in rabbits, and histological analysis showed no effect or damage to rabbit eyeballs. Cmax and the AUC0–24 were higher in LORA-NLCs Ocugel compared with pure Lora dispersion-loaded gel The research findings confirmed that NLCs could enhance solubility, trans-corneal penetrability, and the bioavailability of LORA.

Introduction: This study was proposed to assess the potential role of efflux transporters in reversing fluconazole resistance in Candida glabrata isolates treated with fluconazole loaded nanostructured lipid carriers (FLZ-NLCs). Methods: The ultrasound technique was used to synthesize the FLZ-NLCs. Four fluconazole-resistant, as well as one susceptible standard C. glabrata isolates, were applied and exposed to FLZ/ FLZ-NLCs for 20 h at 37°C. Real-time PCRs were done to estimate the likely changes in ATP-binding cassette transporter genes. Results: Similar to the FLZ-exposed-susceptible standard strain which showed no alteration, the genes were not up-regulated significantly under the FLZ-NLCs treated condition. While they were over-expressed when the yeasts were treated with fluconazole. Conclusion: It is highly suggested that due to the nature of the NLCs which shields the whole conformation of the drug, FLZ is not recognized by the efflux transporter subunits and consequently the translocation would not happen.

Abstract Background Allopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo. Methodology ALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension. Results The optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague–Dawley rats after transdermal administration as compared to oral ALP suspension. Conclusion ALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

Purpose: To investigate the in vitro anti-skin-aging properties of Cratoxylum formosumextract and encapsulate this plant extract in nanostructured lipid carriers (CFE-NLCs) fordermal application.Methods: The biological properties of the plant extract, including enhanced procollagen typeI synthesis and anti-matrix metalloproteinase activity, were evaluated to assess its cosmeticbenefits. An artificial neural network (ANN) coupled with K-fold cross-validation was appliedto investigate the effects of the formulants and optimize the CFE-NLCs. The physicochemicalproperties, percutaneous absorption, and irritation potential of the CFE-NLCs were analyzed.Results: Liquid chromatography-mass spectrometry analysis revealed that CFE contained5-O-caffeoylquinic acid as the vital constituent. Appropriate skin-care properties were alsodemonstrated with respect to enhanced type I procollagen synthesis and the inhibition of MMP-1, MMP-3, and MMP-9 in primary human dermal fibroblasts. The optimal CFE-NLCs exhibitedbetter skin absorption and biocompatibility and lower irritation potential than the free botanicalextract solution.Conclusion: The findings obtained highlight CFE-NLCs as promising skin-care ingredients.

Synthesis of targeted nanostructure lipid carriers for stylosin (STY-CFN-NPs) delivery to MCF-7 cells. STY-CFN-NPs were formulated via the homogenization and ultra-sonication technique. After evaluating the amount of drug encapsulation and FA binding, the toxicity effect of the STY and STY-CFN-NPs on MCF-7 cells was measured by the MTT method. Cell cycle analysis, AO/PI staining and qPCR to assess the inducing of apoptosis as well as Tubo cancer cell inoculated mouse model for antitumor properties of STY-CFN-NPs were used. Significant increases in nanoparticle size and changes in zeta potential were observed after FA-CS coating on nanoparticles. Slow release of the STY within 144 h as well as the acceptable rate for STY encapsulation efficiency (92.4% and FA binding (52.5%) to the STY-CFN-NPs (PS: 66.26 ± 3.02 nm, ZP: 29.54 ± 1.01 mV and PDI: 0.32 ± 0.01) was reported. STY-CFN-NPs exhibited higher toxicity compared to STY suspension and treatment with STY-CFN-NPs was lead to increased apoptotic cells, stopped cells in the SubG1 phase, and also increased caspase and BAX expression and decreased BCL-2 and BCL-XL expression in in vitro and decreased the size of murine tumors (54.57% in 16 days) in in vivo. The results showed STY-CFN-NPs have good potential for breast cancer management. [ABSTRACT FROM AUTHOR]

Unsuccessful anesthesia often occurs under an inflammatory tissue environment, making dentistry treatment extremely painful and challenging. Articaine (ATC) is a local anesthetic used at high (4%) concentrations. Since nanopharmaceutical formulations may improve the pharmacokinetics and pharmacodynamics of drugs, we encapsulated ATC in nanostructured lipid carriers (NLCs) aiming to increase the anesthetic effect on the inflamed tissue. Moreover, the lipid nanoparticles were prepared with natural lipids (copaiba (Copaifera langsdorffii) oil and avocado (Persia gratissima) butter) that added functional activity to the nanosystem. NLC-CO-A particles (~217 nm) showed an amorphous lipid core structure according to DSC and XDR. In an inflammatory pain model induced by λ-carrageenan in rats, NLC-CO-A improved (30%) the anesthetic efficacy and prolonged anesthesia (3 h) in relation to free ATC. In a PGE2-induced pain model, the natural lipid formulation significantly reduced (~20%) the mechanical pain when compared to synthetic lipid NLC. Opioid receptors were involved in the detected analgesia effect since their blockage resulted in pain restoration. The pharmacokinetic evaluation of the inflamed tissue showed that NLC-CO-A decreased tissue ATC elimination rate (ke) by half and doubled ATC's half-life. These results present NLC-CO-A as an innovative system to break the impasse of anesthesia failure in inflamed tissue by preventing ATC accelerated systemic removal by the inflammatory process and improving anesthesia by its association with copaiba oil. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to characterize the undecylenoyl phenylalanine (Sepiwhite (SEPI))-loaded nanostructured lipid carriers (NLCs) as a new antimelanogenesis compound. Methods: In this study, an optimized SEPI-NLC formulation was prepared and characterized for particle size, zeta potential, stability, and encapsulation efficiency. Then, in vitro drug loading capacity and the release profile of SEPI, and its cytotoxicity were investigated. The ex vivo skin permeation and the anti-tyrosinase activity of SEPI-NLCs were also evaluated. Results: The optimized SEPI-NLC formulation showed the size of 180.1 ± 5.01 nm, a spherical morphology under TEM, entrapment efficiency of 90.81 ± 3.75%, and stability for 9 months at room temperature. The differential scanning calorimetry (DSC) analysis exhibited an amorphous state of SEPI in NLCs. In addition, the release study demonstrated that SEPI-NLCs had a biphasic release outline with an initial burst release compared to SEPI-EMULSION. About 65% of SEPI was released from SEPI-NLC within 72 h, while in SEPI-EMULSION, this value was 23%. The ex vivo permeation profiles revealed that the higher SEPI accumulation in the skin following application of SEPI-NLC (up to 88.8%) compared to SEPI-EMULSION (65%) and SEPI-ETHANOL (74.8%) formulations (P < 0.01). An inhibition rate of 72% and 65% was obtained for mushroom and cellular tyrosinase activity of SEPI, respectively. Moreover, results of in vitro cytotoxicity assay confirmed SEPI-NLCs to be non-toxic and safe for topical use. Conclusion: The results of this study demonstrate that NLC can efficiently deliver SEPI into the skin, which has a promise for topical treatment of hyperpigmentation. [ABSTRACT FROM AUTHOR]

Cancer is a life-threatening disease that is associated with persistent tissue injury and uncontrolled cell growth. The treatments available to treat cancer are chemotherapy, surgery and radiation therapy. These treatments are used in combinations, while the most preferred treatment is chemotherapy. Because of the Non-specificity of anticancer drugs, they kill normal healthy cells along with cancer cells which lead to severe side effects. To minimize such limitations associated with conventional chemotherapy, nanostructured lipids carriers can be developed. These are nanocarriers consisting of a mixture of solid and liquid lipids along with surfactants. Lipids used in the formulation of NLCs are biocompatible and biodegradable. NLCs ensure high drug payload, less drug expulsion and more stability on storage. NLCs enhance the aqueous solubility of lipophilic anticancer drugs. Their surface modification can help to overcome drug resistance in cancer therapy. Controlled and targeted drug delivery of anticancer drugs can be possible by formulating them as NLCs. NLCs can play an important role in targeting anticancer drugs by different mechanisms. This review highlights types, formulation methods, characterization of nanostructured lipid carriers and strategies to achieve targeted release of anticancer drugs loaded in NLCs. [ABSTRACT FROM AUTHOR]

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye. [ABSTRACT FROM AUTHOR]

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are receiving increasing interest as an approach to encapsulate natural extracts to increase the physicochemical stability of bioactives. Cannabis extract-derived cannabidiol (CBD) has potent therapeutic properties, including anti-inflammatory, antioxidant, and neuroprotective properties. In this work, physicochemical characterization was carried out after producing Compritol-based nanoparticles (cSLN or cNLC) loaded with CBD. Then, the determination of the encapsulation efficiency (EE), loading capacity (LC), particle size (Z-Ave), polydispersity index (PDI), and zeta potential were performed. Additionally, the viscoelastic profiles and differential scanning calorimetry (DSC) patterns were recorded. As a result, CBD-loaded SLN showed a mean particle size of 217.2 ± 6.5 nm, PDI of 0.273 ± 0.023, and EE of about 74%, while CBD-loaded NLC showed Z-Ave of 158.3 ± 6.6 nm, PDI of 0.325 ± 0.016, and EE of about 70%. The rheological analysis showed that the loss modulus for both lipid nanoparticle formulations was higher than the storage modulus over the applied frequency range of 10 Hz, demonstrating that they are more elastic than viscous. The crystallinity profiles of both CBD-cSLN (90.41%) and CBD-cNLC (40.18%) were determined. It may justify the obtained encapsulation parameters while corroborating the liquid-like character demonstrated in the rheological analysis. Scanning electron microscopy (SEM) study confirmed the morphology and shape of the developed nanoparticles. The work has proven that the solid nature and morphology of cSLN/cNLC strengthen these particles' potential to modify the CBD delivery profile for several biomedical applications. [ABSTRACT FROM AUTHOR]

Although curcumin is a commonly used antioxidant in cosmetic and pharmaceutical products, the dermal efficacy of curcumin is limited due to its very low solubility and poor permeability. Considering dermal application, lipid-based nanocarriers (LbNs) are highlighted as promising delivery systems for enhancing the efficacy of active substances. The aim of this study is to evaluate the effect of the components of LbNs on the antioxidant activity of curcumin. For this purpose, the mixture of Precirol® ATO5 and Tristearin was selected as solid lipid; while vitamin E, pomegranate seed oil (PSO) and Labrafac® Lipophile WL 1349 were used as liquid lipids. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) formulations were designed by using different combination of these lipids and Gelucire®50/13 as an amphiphilic surfactant. The particle size, PDI, zeta potential analysis, encapsulation efficiency and in-vitro release studies were performed as particle characteristics. The contribution of LbNs with different structures to the antioxidant capacity of curcumin was evaluated by in-vitro ABTS scavenging experiment. While SLN has an average particle size of 106.7 nm with negative zeta potential, the size of NLC and NE formulations were below 100nm. The highest curcumin release upon 24h was obtained by NLC formulation prepared with PSO. A significant contribution to the antioxidant activity of curcumin was obtained when vitamin E and PSO were used as liquid lipid in NLC and NE formulations. In conclusion, it is possible to improve the antioxidant effect of curcumin by the modification of the structure of LbNs. [ABSTRACT FROM AUTHOR]

In this study, a novel bioadhesive material, a conjugate of chondroitin sulfate and L-cysteine (CS-Cys), was synthesized and modified on the surface of the cationic nanostructured lipid carriers loaded dexamethasone to prepare a novel nano-lipid ocular delivery system (Dex-CS-Cys-cNLC). Through the permeation and retention studies of isolated cornea, it was demonstrated that Dex-CS-Cys-cNLC has better corneal permeation and retention ability and can better overcome the barrier effect of the ocular surface. In addition, the fluorescent probe (RhB) was used to replace the drug, and fluorescence imaging was used to investigate the ocular surface retention ability of the formulation, and the results showed that CS-Cys-cNLC has stronger retention ability and can effectively prolong the time of drug action in the ocular surface. Dex-CS-Cys-cNLC was not irritating to rabbit eye tissues and was a safe delivery system. The results of rabbit dry eye pharmacodynamic experiments also showed that Dex-CS-Cys-cNLC could effectively alleviate dry eye symptoms in rabbits, effectively repair corneal damage, and improve the stability of tear film. All these experimental results suggest that Dex-CS-Cys-cNLC is a promising drug delivery carrier for the treatment of anterior segment of the eye disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to encapsulate cannabidiol (CBD) extract in nanostructured lipid carriers (NLCs) to improve the chemical stability and anti-inflammatory activity of CBD for dermal delivery. CBD-loaded NLCs (CBD-NLCs) were prepared using cetyl palmitate (CP) as a solid lipid and stabilized with Tego® Care 450 (TG450) or poloxamer 188 (P188) by high-pressure homogenization (HPH). The CBD extract was loaded at 1% w/w. Three different oils were employed to produce CBD-NLCs, including Transcutol® P, medium-chain triglycerides (MCT), and oleic acid (OA). CBD-NLCs were successfully prepared with an entrapment efficiency (E.E.) of 100%. All formulations showed particle sizes between 160 and 200 nm with PDIs less than 0.10. The type of surfactant and oil used affected the particle sizes, zeta potential, and crystallinity of the CBD-NLCs. CBD-NLCs stabilized with TG450 showed higher crystallinity after production and storage at 30 °C for 30 days as compared to those with P188. Encapsulation of the CBD extract in NLCs enhanced its chemical stability after exposure to simulated sunlight (1000 kJ/m2) compared to that of the CBD extract in ethanolic solution. The CBD-NLCs prepared from MCT and OA showed slower CBD release compared with that from Transcutol® P, and the kinetic data for release of CBD from CBD-NLCs followed Higuchi's release model with a high coefficient of determination (>0.95). The extent of CBD permeation through Strat-M® depended on the oil type. The cytotoxicity of the CBD extract on HaCaT and HDF cells was reduced by encapsulation in the NLCs. The anti-inflammatory activity of the CBD extract in RAW264.7 cell macrophages was enhanced by encapsulation in CBD-NLCs prepared from MCT and OA. [ABSTRACT FROM AUTHOR]

Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood–brain barrier (BBB). The growing availability of innovative excipients/ligands allowing improved brain targeting and controlled drug release makes the lipid nanocarriers a reasonable choice to overcome the factors impeding drug delivery through the BBB. However, a wide variety of methods, study designs and experimental conditions utilized in the literature hinder their systematic comparison, and thus slows the advances in brain-targeting by lipid-based nanoparticles. This review provides an overview of the methods most commonly utilized during the preclinical testing of liposomes, nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers intended for the treatment of various CNS disorders via the parenteral route. In order to fully elucidate the structure, stability, safety profiles, biodistribution, metabolism, pharmacokinetics and immunological effects of such lipid-based nanoparticles, a transdisciplinary approach to preclinical characterization is mandatory, covering a comprehensive set of physical, chemical, in vitro and in vivo biological testing. [ABSTRACT FROM AUTHOR]

Marine sources contain several bioactive compounds with high therapeutic potential, such as remarkable antioxidant activity that can reduce oxidative stress related to the pathogenesis of neurodegenerative diseases. Indeed, there has been a growing interest in these natural sources, especially those resulting from the processing of marine organisms (i.e., marine bio-waste), to obtain natural antioxidants as an alternative to synthetic antioxidants in a sustainable approach to promote circularity by recovering and creating value from these bio-wastes. However, despite their expected potential to prevent, delay, or treat neurodegenerative diseases, antioxidant compounds may have difficulty reaching the brain due to the need to cross the blood–brain barrier (BBB). In this regard, alternative delivery systems administered by different routes have been proposed, including intranasal administration of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which have shown promising results. Intranasal administration shows several advantages, including the fact that molecules do not need to cross the BBB to reach the central nervous system (CNS), as they can be transported directly from the nasal cavity to the brain (i.e., nose-to-brain transport). The benefits of using SLN and NLC for intranasal delivery of natural bioactive compounds for the treatment of neurodegenerative diseases have shown relevant outcomes through in vitro and in vivo studies. Noteworthy, for bioactive compounds obtained from marine bio-waste, few studies have been reported, showing the open potential of this research area. This review updates the state of the art of using SLN and NLC to transport bioactive compounds from different sources, in particular, those obtained from marine bio-waste, and their potential application in the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Psoriasis is linked with unusual differentiation and hyperproliferation of epidermal keratinocytes that significantly impair the quality of life (QoL) of patients. The present treatment options only provide symptomatic relief and are surrounded by various adverse effects. Recently, nanostructured lipid carriers (NLCs) have emerged as next-generation nanocarriers with better physicochemical characteristics. The current manuscript provides background information on psoriasis, its pathophysiology, existing treatment options, and its limitations. It highlights the advantages, rationale, and mechanism of the permeation of NLCs for the treatment of psoriasis. It further gives a detailed account of various NLC nanoformulations for the treatment of psoriasis. In addition, tabular information is provided on the most relevant patents on NLCs for treating psoriasis. Lastly, light is shed on regulatory considerations related to NLC-like nanoformulations. In the treatment of psoriasis, NLCs display a sustained release drug profile, an ability to incorporate both hydrophobic and hydrophilic drugs, an enhancement in skin hydration, penetrability, retention, and bioavailability of the drug, along with reduced staining potential as compared to conventional ointments, and decreased side effects of drug molecules. This affirms the bright future of NLC nanoformulations in the treatment of psoriasis. However, academic industry collaboration and more sound regulatory controls are required to commercialize the NLC nanoformulations for psoriasis treatment. [ABSTRACT FROM AUTHOR]