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In this research, nanostructured lipid carriers (NLCs) loaded with limonene were developed using various solid lipids. The impact of high temperatures on the characteristics of NLCs was investigated. NLCs exhibited zeta potential values exceeding |30| mV, indicating excellent homogeneity and stability. Increasing the carbon chain length of monoglycerides from C15 to C21 resulted in a corresponding increase in particle size of NLCs from 219.1 ± 1.1 to 243.3 ± 0.9 nm. However, the particle size remained relatively constant with an increase in the number of solid lipid carbon chains. Encapsulation efficiency of limonene increased from 66.0 ± 0.7% to 86.2 ± 0.8% with an increase in the number of solid lipid carbon chains. The result showed that more ester bonds facilitated the dissolution of the target and enhanced the interaction forces between solid lipids and the target. X‐ray diffraction, Fourier transform‐infra‐red spectroscopy and differential scanning calorimetry analyses confirmed effective encapsulation of limonene in NLCs, resulting in good stability. NLCs prepared from various solid lipids exhibited varying properties. Glycerol triglyceride demonstrated superior stability and homogeneity of nanoparticles under high‐temperature conditions compared to other solid lipids. This study provides enhancing the thermal stability of limonene‐loaded NLCs and proposes a novel approach for their practical application. [ABSTRACT FROM AUTHOR]

This study explored the combined administration of docetaxel (DOC) and erlotinib (ERL) using nanostructured lipid carriers (NLCs), with folic acid (FA) conjugation to enhance their synergistic anticancer efficacy against triple-negative breast cancer. NLCs were developed through hot melt homogenization–ultrasound dispersion, and optimized by a quality-by-design (QbD) approach using Plackett–Burman design and Box–Behnken design. Plots were generated based on maximum desirability. Spherical, nanosized dispersions (<200 nm) with zeta potential ranging from −16.4 to −14.15 mV were observed. These nanoformulations demonstrated ~95% entrapment efficiency with around 5% drug loading. Stability tests revealed that the NLCs remained stable for 6 months under storage conditions at 4 °C. In vitro release studies indicated sustained release over 24 h, following Higuchi and Korsmeyer–Peppas models for NLCs and FA NLCs, respectively. Additionally, an in vitro pH-stat lipolysis model exhibited a nearly fivefold increase in bioaccessibility compared to drug-loaded suspensions. The DOC–ERL-loaded formulations exhibited dose- and time-dependent cytotoxicity, revealing synergism at a 1:3 molar ratio in MDA-MB-231 and 4T1 cells, with combination indices of 0.35 and 0.37, respectively. Co-treatment with DOC–ERL-loaded FA NLCs demonstrated synergistic anticancer effects in various in vitro assays. [ABSTRACT FROM AUTHOR]

The objective of this investigation was to formulate an ideal nanostructured lipid carrier (NLC) for glib-enclamide in oral capsules. Employing factorial design, the NLC formulation was achieved through high-pressure homogenization using Design-Expert® software, optimized using a 32-factor experimental design and response surface analysis. Comprehensive analyses were conducted to characterize NLCs and determine the optimal formulation. Rigorous evaluations, including drug content, in vitro diffusion and stability studies, were performed. Safety assessments, efficacy studies and optimization led to the identification of an optimal NLC formulation with specific lipid and surfactant percentages, resulting in a desirable particle size (nm) and a robust zeta potential indicative of strong physical stability. [ABSTRACT FROM AUTHOR]

Donepezil hydrochloride (DPL) and Embelin (EMB) loaded Nanostructured Lipid Carriers (NLCs) have been developed and optimized to achieve optimal drug loading, safer nasal delivery, effective neuronal/cell uptake, enhanced brain accessibility, controlled release, and desired therapeutic effect. Molecular docking studies demonstrated that both drugs bind effectively to AchE with interaction energies of -48.5319 and − 65.7525, respectively, indicating a synergistic approach. The hydrophobic interactions with target proteins facilitate the transportation of drugs through brain hydrophobic channels to provide a desired pharmacological response. N2a cell line investigation advised a 1:1 ratio of DPL and EMB to have the greatest possible synergistic effect based on the MTT assay. NLCs were fabricated by hot emulsification probe sonication method and optimized using QbD-based Central Composite Rotatable Design (CCRD). Optimized NLCs with a diameter of 180.2 nm were suitable for axonal uptake. A low Polydispersity index (PDI) score of 0.37 and Zeta Potential (ZP) of -12 mV indicated a uniform monodisperse system with persistent and stable dispersion properties. The NLCs demonstrated sustained drug release, DPL released at 90.72 ± 1.00%, and EMB at 81.30 ± 0.52% in 24 h. The Korsemeyer-Peppas model proved to be the most accurate fit due to its strong correlation. Ex vivo permeation and CLSM studies revealed superior goat nasal mucosa penetration of NLCs over suspension with a higher fluorescence level, up to 35 μm. NLCs treated nasal mucosa exhibited no erosion or interstitial gaps in the histopathological study. Moreover, NLCs were nontoxic and non-irritating, with a HET CAM score of 0.68 ± 0.05, indicating safe nasal delivery. The cellular uptake study showed a preponderance of the NLCs in the Cell's cytoplasm, indicating ready uptake by N2a cells. Hence, intranasal therapy with the DPL and EMB-loaded NLCs could be a practical and promising implementation. Further in vivo, and clinical studies will be required to establish the formulation's efficacy in treating Alzheimer's disease (AD). Graphical Abstract [ABSTRACT FROM AUTHOR]

Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis. [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 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]

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]

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]

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]

Purpose: Asiatic acid (AA) is reported for its neuroprotective potential in Alzheimer's disease (AD). This present work aimed to develop AA loaded nanostructured lipid carriers (AAN) for targeting the delivery of AA into the brain and ameliorating the cognitive deficits in AD rats. Methods: AAN was optimized using the Box-Behnken design, considering 3 factors (soya lecithin, tween 80, and high pressure homogenizer (HPH) pressure) as independent variables while particle size (PS), zeta potential (ZP) and entrapment efficiency (EE) were dependent variables. Cytotoxicity assay and internalization studies of AAN were evaluated in SH-SY5Y cells and further neuroprotective efficiency on intracellular amyloid beta (Aβ) aggregation was evaluated in Aβ 1–42 treated cells with thioflavin T (ThT). The behavioral acquisition effects were evaluated in Aβ 1–42 (5 µg/ 5 µL, intracerebroventricular (ICV), unilateral) induced AD model followed by the histology and quantification of neurotransmitters levels. Results: The optimized AAN revealed desired PS (44.1 ± 12.4 nm), ZP (- 47.1 ± 0.017 mv) and EE (73.41 ± 2.53%) for brain targeting delivery of AA. In-vitro, AAN exhibited better neuroprotective potential than AA suspension (AAS). AA content was 1.28 folds and 2.99 folds heightened in plasma and brain respectively after the i.p. administration of AAN as compared to AAS. The results of pharmacodynamic studies manifested the AAN treatment significantly (p < 0.05) ameliorated the cognitive deficits. Conclusions: Hence, developed AAN has neuroprotective potential and should be further considered as an unconventional platform in preclinical model for the management of AD. [ABSTRACT FROM AUTHOR]

Purpose: The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods: Mono‐delivery and co‐delivery of SRL and CsA by NLCs (S‐NLCs, C‐NLCs, and S‐C‐NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results: Well‐designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co‐delivery by NLCs. Following S‐NLCs and C‐NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro‐inflammatory cytokines (IFN‐γ, TNF‐α, IL‐17, and IL‐21) and their regulators (T‐bet and RORγt), as well as a lower level of an anti‐inflammatory cytokine (IL‐10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S‐C‐NLCs intervention. Conclusions: S‐C‐NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance. [ABSTRACT FROM AUTHOR]

[Display omitted] Combined usage of Layer-by-Layer (LbL) coating and alkaline phosphatase (ALP) - responsive charge reversal strategies can improve the cellular internalisation of the colloidal drug delivery systems by also decreasing their cytotoxic effects. Anionic core NLCs were formed by combining the melt emulsification method and ultrasonication. The resulting core NLCs were coated sequentially first with protamine (Prot NLCs) and then with sodium tripolyphosphate (TPP) or sodium polyphosphate (Graham's salt, PP) generating TPP or PP NLCs, respectively. The developed NLCs were characterised regarding their size and zeta potential. Enzyme-induced charge reversal of the TPP and PP NLCs was evaluated by zeta potential measurements upon their incubation with alkaline phosphatase (ALP). In parallel, time-dependent phosphate release was monitored in the presence of isolated as well as cell-associated ALP. Morphological evaluations were performed by scanning electron microscopy (SEM) studies. Moreover, cell viability and cellular uptake studies were carried out in vitro on Caco-2 cells. The core NLCs were obtained with a mean size of 272.27 ± 5.23 nm and a zeta potential of −25.70 ± 0.26 mV. Upon coating with protamine, the zeta potential raised to positive values with a total change up to Δ29.3 mV also displaying an increase in particle size. The second layer coating with TPP and PP provided a negative surface charge. Subsequent to ALP treatment, the zeta potential of the TPP and PP NLCs reversed from negative to positive values with total changes of Δ8.56 and Δ7.47 mV, respectively. Conformably, significant amounts of phosphate were released from both formulations. Compared with core NLCs, improved cellular viability as well as increased cellular uptake were observed in case of Prot, TPP and PP NLCs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs). Methods: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined. Results: The PS, ZP and EE were found to be 85.26 nm, −23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed. Conclusion: The outcomes of study deciphered successful formulation of Mes-Cur NLCs. [ABSTRACT FROM AUTHOR]

Schematic representation of functional pattern of Magnolol-NLC against Chronic obstructive pulmonary disease. (Created with BioRender, agreement number: AI272U59N1). [Display omitted] Chronic obstructive pulmonary disease (COPD) is a prevalent lung condition characterized by airflow obstruction, disability, and high mortality rates. Magnolol (MA), known for its anti-inflammatory and antioxidant properties, holds the potential for alleviating COPD symptoms. However, MA faces challenges like poor aqueous solubility and low bioavailability. Herein MA-loaded nanostructured lipid carriers (MA-NLC) were prepared using emulsification and solvent evaporation. These carriers exhibited a particle size of (19.67 ± 0.36) nm, a polydispersity index of (0.21 ± 0.01), and a zeta potential of (−5.18 ± 0.69) mV. The fine particle fraction of MA-NLC was (68.90 ± 0.07)%, indicating minimal lung irritation and enhanced safety. Pulmonary delivery of MA-NLC via nebulizer actively targeted the diseased lung tissues, facilitated slow release, and overcame the challenges of low oral absorption and bioavailability associated with MA. This formulation prolonged the residence time of MA and optimized its therapeutic effect in pulmonary tissues. Upon pulmonary administration, MA-NLC effectively regulated inflammatory and oxidative stress markers in COPD models, demonstrating its potential as a promising therapeutic platform for COPD management. [ABSTRACT FROM AUTHOR]

Whiteleg shrimp (Penaeus vannamei) have been vulnerable to the stress induced by different aquaculture operations such as capture, handling, and transportation. In this study, we developed a novel clove oil-nanostructured lipid carrier (CO-NLC) to enhance the water-soluble capability and improve its anesthetic potential in whiteleg shrimp. The physicochemical characteristics, stability, and drug release capacity were assessed in vitro. The anesthetic effect and biodistribution were fully investigated in the shrimp body as well as the acute multiple-dose toxicity study. The average particle size, polydispersity index, and zeta potential value of the CO-NLCs were 175 nm, 0.12, and −48.37 mV, respectively, with a spherical shape that was stable for up to 3 months of storage. The average encapsulation efficiency of the CO-NLCs was 88.55%. In addition, the CO-NLCs were able to release 20% of eugenol after 2 h, which was lower than the standard (STD)-CO. The CO-NLC at 50 ppm observed the lowest anesthesia (2.2 min), the fastest recovery time (3.3 min), and the most rapid clearance (30 min) in shrimp body biodistribution. The results suggest that the CO-NLC could be a potent alternative nanodelivery platform for increasing the anesthetic activity of clove oil in whiteleg shrimp (P. vannamei). [ABSTRACT FROM AUTHOR]

This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization–sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance. [ABSTRACT FROM AUTHOR]

Migraine is a severe neurovascular disease manifested mainly as unilateral throbbing headaches. Triptans are agonists for serotonin receptors. Zolmitriptan (ZMP) is a biopharmaceutics classification system (BCS) class III medication with an absolute oral bioavailability of less than 40%. As a result, our research intended to increase ZMP bioavailability by developing transdermal nanostructured lipid carriers (NLCs). NLCs were prepared utilizing a combination of hot melt emulsification and high-speed stirring in a 32 full factorial design. The studied variables were liquid lipid type (X1) and surfactant type (X2). The developed NLCs were evaluated in terms of particle size (Y1, nm), polydispersity index (Y2, PDI), zeta potential (Y3, mV), entrapment efficacy (Y4, %) and amount released after 6 h (Q6h, Y5, %). At 1% Mygliol as liquid lipid component and 1% Span 20 as surfactant, the optimized formula (NLC9) showed a minimum particle size (138 ± 7.07 nm), minimum polydispersity index (0.39 ± 0.001), acceptable zeta potential (−22.1 ± 0.80), maximum entrapment efficiency (73 ± 0.10%) and maximum amount released after 6 h (83.22 ± 0.10%). The optimized formula was then incorporated into gel preparation (HPMC) to improve the system stability and ease of application. Then, the pharmacokinetic study was conducted on rabbits in a cross-over design. The calculated parameters showed a higher area under the curve (AUC0–24, AUC0–∞ (ng·h/mL)) of the developed ZMP-NLCs loaded gel, with a 1.76-fold increase in bioavailability in comparison to the orally administered marketed product (Zomig®). A histopathological examination revealed the safety of the developed nanoparticles. The declared results highlight the potential of utilizing the proposed NLCs for the transdermal delivery of ZMP to improve the drug bioavailability. [ABSTRACT FROM AUTHOR]

Maduramicin ammonium (MAD) is one of the most frequently used anticoccidial agents in broiler chickens. However, the high toxicity and low solubility of MAD limit its clinical application. In this study, MAD-loaded nanostructured lipid carriers (MAD–NLCs) were prepared to overcome the defects of MAD by using highly soluble nanostructured lipid carriers (NLCs). The formulation was optimized via a three-level, three-factor Box–Behnken response surface method. Then, the optimal MAD–NLCs were evaluated according to their hydrodynamic diameter (HD), zeta potential (ZP), crystal structure, encapsulation efficiency (EE), drug loading (DL), in vitro release, and anticoccidial effect. The optimal MAD–NLCs had an HD of 153.6 ± 3.044 nm and a ZP of −41.4 ± 1.10 mV. The X-ray diffraction and Fourier-transform infrared spectroscopy results indicated that the MAD was encapsulated in the NLCs in an amorphous state. The EE and DL were 90.49 ± 1.05% and 2.34 ± 0.04%, respectively, which indicated that the MAD was efficiently encapsulated in the NLCs. In the in vitro study, the MAD–NLCs demonstrated a slow and sustained drug release behavior. Notably, MAD–NLCs had an excellent anticoccidial effect against Eimeria tenella in broiler chickens. In summary, MAD–NLCs have huge potential to form a new preparation administered via drinking water with a powerful anticoccidial effect. [ABSTRACT FROM AUTHOR]

[Display omitted] Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV–Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and −5.80 mV - −18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment. [ABSTRACT FROM AUTHOR]

Objective(s): The optimal formulation of Nanostructured lipid carriers (NLCs) that contains argan oil and caffeine was considered to be developed as a topical treatment for hair loss. Materials and Methods: 26 batches were prepared according to the central composite design. Dynamic light scattering technique showed size, polydispersity index (PDI), and zeta potential, and electron microscopy depicted the morphology of NLCs. Caffeine encapsulation efficiency (EE) was measured by UV/Vis spectroscopy. Fourier-transform infrared spectroscopy (FTIR) was applied to show caffeine and NLCs interactions. The caffeine invivo morin model was designed to determine the caffeine penetration into follicles and stratum corneum. Results: The optimal formulation consisted of 2% lipid, 2% surfactant, stearic acid/argan oil ratio of 3.5, and span/tween ratio of 1.25. Its spherical NLCs size, PDI, and zeta potential were 256.2 nm, 0.225, and -25.4 respectively. The caffeine EE% was 89% which was homogenously encapsulated in NLCs as shown in FTIR analysis. In vivo studies showed these nanoparticles have the ability to accumulate in the hair follicles by the time. Conclusion: The NLC formulation optimized in this study is a potential formulation for intrafollicular delivery of caffeine. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLC) have been widely studied as delivery systems for a variety of routes, including the skin. Their composition results in an imperfect lipid matrix, allowing increased drug encapsulation. Allopurinol (AP), a xanthine oxidase inhibitor, is characterized by low water solubility and high melting point, which has hampered its use through the topical route. In this work, AP was incorporated in a NLC formulation to enhance drug-carrier association and skin delivery as a topical approach to treat wounds. AP-NLC system was characterized in terms of size, charge, rheological behavior, and in vitro skin permeation. The in vitro cytotoxicity was evaluated using HaCaT cells. The wound healing efficacy of the AP-NLC formulation on animal skin lesions was evaluated in male Wistar rats. The AP-NLC presented a mean size of 193 ± 15 nm with a PdI of 0.240 ± 0.02, zeta potential values around -49.6 mV, and an encapsulation efficiency of 52.2%. The AP-NLC formulation presented an adequate profile to be used topically, since epidermal and dermal drug retention were achieved. No reduction in HaCaT cells viability was observed at the tested concentrations (AP < 10 µg/mL). The in vivo application of the AP-NLC formulation resulted in the regeneration of skin lesions when compared with non-treated controls. [ABSTRACT FROM AUTHOR]

Purpose: Eplerenone (EPL) is a selective mineralocorticoid receptor antagonist used for treatment of chronic central serous chorioretinopathy which characterized by accumulation of subretinal fluid causing a localized area of retinal detachment. unfortunately, EPL suffers from poor oral bioavailability due to poor aqueous solubility in addition to high hepatic first pass metabolism. Method: Aiming to improve its oral bioavailability, EPL-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification solvent evaporation method and in-vitro evaluated for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). A D-optimal design was used for study the effect of liquid lipid to solid lipid ratio, surfactant type and percentage on PS, PDI, EE%, and for data optimization. The optimized EPL-loaded NLCs system was further evaluated using in-vitro drug release and ex-vivo permeation studies through rabbit intestine in comparison to EPL aqueous suspension. The physicochemical properties of the drug in the optimized system were further examined using FT-IR and X-ray diffraction studies. Results: The resultant NLCs showed small PS (100.85-346.60 nm), homogenous distribution (0.173-0.624), negatively charged particles (ZP -20.20 to -36.75 mV), in addition to EE% (34.31-70.64%). The optimized EPL-loaded NLCs system with a desirability value of 0.905 was suggested through the Design expertVR software, containing liquid to solid lipid ratio (2:1) in presence of 0.43%w/v PluronicVR F127 as a surfactant. The optimized EPL-loaded NLCs system showed a PS of 134nm and PDI of 0.31, in addition to high EE% (76 ± 6.56%w/w), and ZP (-32.37 mV). The ex-vivo permeation study showed two-fold higher drug permeation through rabbit intestine compared to that from the aqueous drug suspension after 24 h, confirming the ability of optimized EPL-loaded NLCs system as successful oral targeting delivery carrier. Conclusion: Our results pave the way for a new oral nanotherapeutic approach toward CSCR treatment. In-vivo study is currently under investigation. [ABSTRACT FROM AUTHOR]

Many strategies have been developed to overcome the stratum corneum (SC) barrier, including functionalized nanostructures. Chemical penetration enhancers (CPEs) and cell-penetrating peptides (CPP) were applied to decorate nanostructured lipid carriers (NLC) for topical anesthetic and pain relief. A novel pyrenebutyrate (PB-PEG-DSPE) compound was synthesized by the amide action of the carboxylic acid group of PB with the amido groups of DSPE-PEG. PB-PEG-DSPE has a hydrophobic group, hydrophilic group, and lipid group. The lipid group can be inserted into NLC to form PB functional NLC. In order to improve the penetrability, TAT and PB multi-decorated NLC were designed for the delivery of lidocaine hydrochloride (LID) (TAT/PB LID NLC). The therapeutic effects of NLC in terms of in vitro skin penetration and in vivo in animal models were further studied. The size of TAT/PB LID NLC tested by DLS was 153.6 ± 4.3 nm. However, the size of undecorated LID NLC was 115.3 ± 3.6nm. The PDI values of NLC vary from 0.13 ± 0.01 to 0.16 ± 0.03. Zeta potentials of NLC were negative, between -20.7 and -29.3 mV. TAT/PB LID NLC (851.2 ± 25.3 mg/cm²) showed remarkably better percutaneous penetration ability than PB LID NLC (610.7 ± 22.1 mg/cm²), TAT LID NLC (551.9 ± 21.8 mg/cm²) (p<.05) and nonmodified LID NLC (428.2 ± 21.4 mg/cm²). TAT/PB LID NLC exhibited the most prominent anesthetic effect than single ligand decorated or undecorated LID NLC in vivo. The resulting TAT/PB LID NLC exhibited good skin penetration and anesthetic efficiency, which could be applied as a promising anesthesia system. [ABSTRACT FROM AUTHOR]

Burn wound is usually associated by antibiotic-resistant Pseudomonas aeruginosa infection that worsens and complicates its management. An effective approach is to use natural antibiotics such as cinnamon oil as a powerful alternative. This study aims to investigate topical nanostructured lipid carrier (NLC) gel loaded cinnamon oil for Pseudomonas aeruginosa wound infection. A 24 full factorial design was performed to optimize the formulation with particle size 108.48 ± 6.35 nm, zeta potential -37.36 ± 4.01 mV, and EE% 95.39 ± 0.82%. FTIR analysis revealed no excipient interaction. Poloxamer 407 in a concentration 20% w/w NLC gel was prepared for topical application. Drug release exhibited an initial burst release in the first five hours, followed by a slow, sustained release of up to five days. NLC-cinnamon gel has a significant ability to control the drug release with the lowest minimum inhibitory concentration again P. aeruginosa compared to other formulations (p<.05). In vivo study also showed NLC-cinnamon gel effectively healed the infected burned wound after a six-day treatment course with better antibacterial efficacy in burned animal models. Histological examination ensured the tolerability of NLC-cinnamon gel. The results suggest that nanoparticle-based cinnamon oil gel is a promising natural product against antibiotic-resistant strains of P. aeruginosa in wound infection. [ABSTRACT FROM AUTHOR]

As immune adjuvants assisting vaccines, nanoparticle delivery systems have been widely exploited. Squalene, the major ingredient of approved adjuvant MF59, has great potential in activating immune responses. In the current study, model antigen ovalbumin (OVA) was encapsulated into squalene-based nanostructured lipid carriers (NLCs), and the chitosan, a cationic polysaccharide, was used for modifying nanoparticles to develop a functionalized and cationic nanoparticle delivery system (OVA-csNLCs). Firstly, the optimal formulation of csNLCs was successfully screened out, and had hydrodynamic diameter of 235.80 ± 5.99 nm and zeta potential of 34.90 ± 6.95 mV. Then, the generated OVA-csNLCs had no significant difference in hydrodynamic diameter and exhibited lower zeta potential of 19.03 ± 0.31 mV and high encapsulation efficiency of 83.4%. Sucrose (10%, w /w) was selected as optimal lyoprotectant, exhibiting good stability of OVA-csNLCs in the form of freeze-dried powder. More importantly, the OVA-csNLCs effectively promoted OVA antigen uptake by macrophage, significantly enhanced the level of OVA-specific IgG, and induced a Th2-based immune response in vivo. Furthermore, mice immunization experiment demonstrated that OVA-csNLCs had well biocompatibility and facilitated spleen lymphocytes proliferation. Above findings indicate that chitosan modified squalene nanostructured lipid carriers show promise as antigen delivery system and an open adjuvant platform. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the effect of high shear homogenization (HSH) and ultrasonication (US) on the physicochemical properties of blank and olanzapine loaded nanostructured lipid carriers (NLCs) along with their drug loading potential and drug release profiles from formulated particles. NLCs were prepared with different ratios of Compritol and Miglyol as the solid and liquid lipids, respectively, under changing HSH and US times between 0 to 15 min. The surfactants (Poloxamer 188 (P188) and tween 80) and the drug content was kept constant in all formulations. The prepared NLCs were evaluated for particle size, polydispersity index, zeta potential, drug crystallinity and chemical interactions between lipids and OLZ. The in-vitro drug release was performed using dialysis tube method in phosphate buffer solution (PBS) at pH 7.4. The formulated NLCs were negatively charged, spherically shaped and monodisperse, with particle sizes ranging from 112 to 191 nm. There was a significant influence of US time on the preparation of NLCs in comparison to HSH, where a significant reduction in the mean particle diameter was seen after 5 min of sonication. An increase of Miglyol content in NLCs led to an increase in particle size. In general, application of US led to decrease in particle size after HSH but an increase in particle diameter of low Miglyol containing preparation was also observed with longer sonication time. OLZ was successfully encapsulated in the NLCs and a total release of 89% was achieved in 24 h in PBS at pH 7.4. [ABSTRACT FROM AUTHOR]

In the present study, mupirocin (MP), an antimicrobial agent, was formulated as a nanostructured lipid carrier (NLC) by using a novel method named as melt emulsion ultrafiltration method. For the formulation of NLC, glyceryl monostearate and watermelon seed oil were used as solid and liquid lipids, respectively. The method was optimized for various parameters by Taguchi design of experiment and prepared NLCs were characterized for particle size, polydispersity index (PDI), shape, zeta potential, % drug loading, and in vitro release profile. The optimized NLCs were found to be smooth, monodisperse with PDI 0.229 ± 0.093. NLCs were found to have an average particle size of 139 ± 0.75 nm and +21.9 ± 0.98 mV as zeta potential. The % drug loading of optimized NLCs was found to be 59% ± 0.13%. The optimized NLCs were able to release the drug up to 24 h. The release kinetic study revealed mixed-order kinetics. Hence, it was concluded that the novel method is simple and able to fabricate MP-loaded NLCs with sustained release property and being stable in terms of particle size, PDI, and % drug loading. [ABSTRACT FROM AUTHOR]

[Display omitted] • Internal structural modulation of nanostructured lipid carriers (NLC). • Hydrogenated soybean phospholipid hindered the NLC polymorphic transition. • Ester bond number of solid lipid affected the crystallization of NLC. In this current study, the internal structure of nanostructured lipid carriers was modulated by phospholipids (lecithin PC, hydrogenated soybean phospholipid HPC) and solid lipids to achieve stable encapsulation of citral. The presence of high melting point HPC could construct α-crystalline type with more lattice defects and effectively inhibit β-ization. The HPC group could maintain the particle size at 155.9–186.9 nm, the polydispersity index (PDI) at 0.182–0.321, the Zeta potential at −57.58 mV to −49.35 mV and the retention rate of citral at 91.33–98.49 % in the acidic environments of 2 mM and 20 mM hydrochloric acid solutions. The recrystallization index (RI) of NLC increased with the number of solid lipid ester bonds (from 3.57 % to 16.58 % in the PC group and from 0.82 % to 12.47 % in the HPC group). The results illustrated that the number of solid lipid ester bonds and the melting point of phospholipids affected crystallinity of the lipid matrix and thus the stability of encapsulated citral. Hydrogenated phospholipid with high melting points was more beneficial in stabilizing citral. The present study improved the acidic stability of citral and provided a new thought for the application of citral in acidic beverages. [ABSTRACT FROM AUTHOR]

Lycopene is one of naturally occurring carotenoids in plants including watermelon (Citrullus lanatus). Heat, light, and oxygen effect on lycopene isomerization and degradation. Nanostructured lipid carriers (NLCs) are drug delivery system which can enhance the stability of active compound. Therefore, this study aimed to develop watermelon extract loaded in NLCs for lycopene stability improvement. The NLCs were prepared using a hot homogenization technique. Cocoa butter was used as solid lipid. Grape seed oil was used as liquid lipid. Span® 80 and Plantasens® HE20 were used as an emulsifier. The selected unloaded NLCs contained solid lipid to liquid lipid at the ratio of 3:1 and 10% (w/w) of total lipid. The particle size of watermelon extract‐loaded NLCs (WH‐loaded NLCs) was 130.17 ± 0.72 nm with low PDI and high zeta potential. It also presented high entrapment efficiency. For stability study, the WH‐NLC3 could enhance stability and maintain lycopene content after stability test. It exhibited the highest values of lycopene content (83.26 ± 2.30%) when stored at 4°C. It also possessed a prolonged release pattern over 48 hr. Therefore, the NLCs could improve stability and release profile of lycopene from watermelon extract. [ABSTRACT FROM AUTHOR]

The main scope of the present investigation was to improve the bioavailability of perphenazine (PPZ) by incorporating it into the nanostructured lipid carriers (NLCs). As a result of lipophilic nature and poor aqueous solubility, as well as extensive hepatic metabolism, PPZ has low systemic bioavailability via the oral route. NLCs have shown potentials to surmount the oral delivery drawbacks of poorly water-soluble drugs. The PPZ-NLCs were prepared by the emulsification-solvent evaporation method and subjected for particle size, zeta potential, and entrapment efficiency (EE) analysis. The optimized NLCs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). Besides, in vitro release behavior, storage stability, and pharmacokinetic studies followed by a single-dose oral administration in rats were performed. Optimized PPZ-NLCs showed a particle size of less than 180 nm with appropriate EE of more than 95%. Microscopic images captured with SEM and TEM exhibited that NLCs were approximately spherical in shape. DSC and PXRD analysis confirmed reduced crystallinity of PPZ after incorporation in NLCs. FTIR spectra demonstrated no chemical interactions between PPZ and NLC components. In vitro release studies confirmed the extended-release properties of NLC formulations. PPZ-NLCs exhibited good stability at 4 °C within three months. The oral bioavailability of NLC-6 and NLC-12 was enhanced about 3.12- and 2.49-fold, respectively, compared to the plain drug suspension. NLC can be designated as an effective nanocarrier for oral delivery of PPZ. [ABSTRACT FROM AUTHOR]

Transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is an effective route of drug administration, as it directs the drug to the inflamed site with reduced incidence of systemic adverse effects such as gastric hemorrhage and ulcers. Tenoxicam (TNX) is a member of NSAIDs that are marketed only as oral tablets due to very poor absorption through the skin. The current study intended to formulate and characterize a hydrogel loaded with nanostructured lipid carriers (NLCs) to enhance the transdermal delivery of TNX. Six formulations of TNX were formulated by slight modifications of high shear homogenization and ultrasonication method. The selected formula was characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo skin permeation studies. Moreover, the effectiveness of the developed formula was studied in-vivo using carrageenan-induced paw edema and hyperalgesia model in irradiated rats. Formula F4 was chosen from six formulations, as the average diameter was 679.4 ± 51.3 nm, PDI value of about 0.02, zeta potential of −4.24 mV, EE of 92.36%, globules nanoparticles without aggregations and absence of interactions in the developed formula. Additionally, the in-vivo study showed the efficacy of formula F4 (TNX-NLCs hydrogel) equivalent to oral TNX in reducing the exaggerated inflammatory response induced by carrageenan after irradiation. In conclusion, the present findings suggest that TNX-NLCs hydrogel could be a potential transdermal drug delivery system alternative to the oral formulation for the treatment of various inflammatory conditions. [ABSTRACT FROM AUTHOR]

The oral delivery of amphotericin B (AmB) has remained a challenge due to its low solubility, permeability, and instability in gastric acidic pH. To solve these issues, herein, we reported a novel approach of using nanostructured lipid carriers (NLCs) and NLCs coating with Eudragit®L100-55 (Eu-NLCs) for the oral delivery of AmB. This study aimed to compare their ability in protecting the drug from degradation in gastrointestinal fluids and permeation enhancement in Caco-2 cells. Uncoated NLCs and Eu-NLCs possessed a mean particle size of ∼180 and ∼550 nm, with a zeta potential of ∼−30 and ∼−50 mV, respectively. Both NLCs demonstrated an AmB entrapment efficiency up to ∼75%. They possessed significantly greater AmB water solubility than the free drug by up to 10-fold. In fasted state simulated gastric fluid, Eu-NLCs provided significantly greater AmB protection from acidic degradation than uncoated NLCs. In fasted state simulated intestinal fluid, both uncoated and Eu-NLCs showed a fast release characteristic. Caco-2 cells permeation studies revealed that uncoated NLCs provided significantly higher apparent permeation coefficient (Papp) value than Eu-NLCs. Moreover, after 6 months of storage at 4 °C in the absence of light, the physicochemical stabilities of the lyophilized uncoated and Eu-NLCs could be maintained. In conclusion, the developed NLCs and Eu-NLCs could be a potential drug delivery system in improving the oral bioavailability of AmB. [ABSTRACT FROM AUTHOR]

NLC containing Gefitinib (NANOGEF) was prepared using stearic acid, sesame oil and surfactants (sodium lauryl sulfate and tween 80). NANOGEFs were evaluated for particle size, polydispersity index (PdI), zeta potential, entrapment efficiency (EE), stability, release studies and cytotoxicity studies (MTT assay). The optimized NANOGEF exhibited particle size of 74.06 ± 9.73 d.nm, PdI of 0.339 ± 0.029 and EE of 99.76 ± 0.015%. The TEM study revealed spherical shape of NANOGEF formulations. The slow and sustained release behavior was exhibited by all NANOGEFs. The effects of surfactants were observed not only on particle size but also on zeta potential, entrapment efficiency, stability and release studies. The MTT assay revealed 4.5 times increase in cytotoxicity for optimized NANOGEF (IC50 = 4.642 µM) when compared with Gefitinib alone (IC50 = 20.88 µM in HCT-116 cells). Thus NANOGEF may be considered as a potential drug delivery system for the cure of colon cancer. [ABSTRACT FROM AUTHOR]

We aimed to develop nanostructured lipid carriers (NLCs) displaying similar characteristics – particle size, polydispersity index, and zeta potential – with the model solid lipid nanoparticles (SLNs) for better comparability. By considering the hydrophilic-lipophilic balance values of solid and liquid lipids, five out of six NLCs and eight out of eight cationic NLCs (cNLCs) were successfully prepared with similar characteristics to their precursor SLN and cationic SLNs (cSLNs), respectively. Among cationic formulations, two cSLNs containing different surfactant/co-surfactant concentrations (4% and 8% S/CoS; w/w) and their cNLC versions prepared with Labrafac lipophile WL 1349 (LWL) or Labrafac PG were selected to compare cytotoxicity, stability, and nucleic acid binding ability. All formulations are well-tolerated by L-929 cells, cSLNs being least toxic. The formulations containing 4% S/CoS had higher stability after 24-months. All nanoparticles formed complexes with pDNA (Binding ability: cNLCs > cSLNs). cSLN and LWL-cNLC containing 4% S/CoS showed the highest pDNA binding capacity in each group, and their spherical/oval shape was revealed by electron microscopy. However, they did not form complexes with siRNA. The developed approach has the potential to simplify the production of (c)NLCs having similar physicochemical properties with the optimum (c)SLN and may provide better insight for (c)SLN vs. (c)NLC comparison studies. [ABSTRACT FROM AUTHOR]

Oral Almotriptan maleate (ALM) is used in the treatment of migraine; however, due to its extreme aqueous solubility, shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. Being flexible and lipophilic in nature, nanostructured lipid carriers (NLCs) represent a promising tool in delivering therapeutic substances to the brain. This investigation is meant to explore the capability of mucoadhesive chitosan-coated NLCs to efficiently deliver ALM to the brain through the nasal route as a non-invasive alternative route for targeting the central nervous system (CNS). D-optimal design was adopted and thirteen different formulae were prepared using hot homogenization and ultrasonication technique; where an accurate amount of the almotriptan was added to the molten lipid mixture followed by the addition of the heated aqueous phase under stirring, then the mixture was subjected to homogenization and ultrasonication. The prepared systems were then assessed for their particle size, PDI (polydispersity index), zeta potential (ZP), and entrapment efficiency (EE). The optimized selected formula; F1; composed of 50/50 Compritol/Labrafil and a co-mixture of 2:1 tween 80: Lauroglycol all coated in chitosan, showed a PS of 255 nm, PDI 0.27, ZP 34.1 mV, and 80% EE. A bi-phasic in vitro drug release pattern was obtained, enhanced mucoadhesive property and ex-vivo permeability through sheep nasal mucosa were attained. The In vivo studies performed on albino rabbits showed significantly higher C max results in plasma of the optimized ALM-NLC (1.54 μg/mL) compared to those of IN ALM solution (0.25 μg/mL) and ALM oral tablet market product (0.58 μg/mL). Brain C max were found to be 3.64 μg/mL, 0.5 μg/mL and 0.48 μg/mL for IN ALM-NLC, oral ALM market product and, IN ALM solution, respectively. Histopathological examination marked the formula as safe. [ABSTRACT FROM AUTHOR]

Background: Nisoldipine is an anti hypertensive drug. Nisoldipine exhibits poor oral bioavailability (5%) because of rapid metabolism in the gut and liver. To overcome hepatic first pass metabolism and to enhance bioavailability, lipid based drug delivery systems (Solid lipid nanoparticles (SLN) and nano structure lipid carriers (NLC)) can be exploited. Objectives: In this work, effort was made to prepare novel particulate carrier systems such as stable Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for transdermal delivery of Nisoldipine (NSP). For this investigation, Carbopol 934 used as gel forming agent for hydrogel preparation. Methods: Aqueous dispersions of lipid nanoparticles made from Dynasan 114, 116, 118 were prepared by hot homogenization technique followed by ultrasonication and then optimized formulations of SLN and NLCs were incorporated into the freshly prepared hydrogels. Prepared lipid nanoparticles were characterized for particle size, zeta potential, entrapment efficiency, stability and in-vitro release profile. Also percutaneous permeation of SLN and NLCs were investigated in rat abdominal skin. Results: Analyzing the particles size by photon correlation spectroscopy (PCS) using Malven zeta sizer, which shows that the SLN and NLCs were in the range of 130-330 nm at room temperature. For all the tested formulations (SLN and NLCs), the entrapment efficiency was 72-97%. In-vitro drug release studies were performed for 24 hr. In these two cases the percentage drug release from gels enriched with SLN/NLC showed sustained release over period of 24 hr. In agreement with these results NSPNLC (Nisoldipine nanostructured lipid carriers) dispersion showed faster release. Formulation E4 showed faster release has less particle size and more zeta potential. Conclusion: Based on these, it was selected for further stability and ex-vivo studies. Both the SLN and NLC showed a sustained drug release over a period of 24 hr, but the sustained effect was more pronounced with the SLN and NLC gel formulations. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to optimize a β‐carotene‐loaded nanostructured lipid carrier (βC‐NLC) using the lipid matrix of palm stearin and palm olein and Tween 80 as a surfactant. The NLC was prepared by using the high shear homogenization method. Box–Behnken Design (BBD) response surface methodology (RSM) was applied to optimize the process and formulation. A three‐factor experimental model was used to optimize the combination of palm stearin ratio (A, %w/w), lipid:surfactant ratio (B, %w/w), and (lipid+surfactant):water ratio (C, %w/w). The formulations were evaluated for their responses on particle size (Y1), polydispersity index (Y2), zeta potential (Y3), and encapsulation efficiency (Y4). Subsequently, Fourier‐transform infrared spectroscopy (FTIR), thermal (DT‐TGA), x‐ray diffraction (XRD), transmission electron microscopy (TEM), and in vitro release (Franz diffusion cell) analyses were utilized to observe the resulting optimum formulation. The optimum formulation was obtained at a combination of A (5.5:4.5), B (1:4.9), and C (24:76) %w/w. This resulted in βC‐NLC having a particle size of 166 nm, polydispersity index of 0.35, zeta potential of −26.9 mV, and an encapsulation efficiency of 91.2%. No strong interaction between different NLC components was observed based on FTIR, DT‐TGA, and XRD profiles. Round‐shaped NLC particles were observed under TEM. Franz diffusion cell observation resulted in diffusion profile of β‐carotene of 110.6 μg cm−2 with a flux of 1.06 (μg cm−2 hour−1). This indicates that palm stearin and palm olein can be prospectively developed as βC‐NLC. [ABSTRACT FROM AUTHOR]

The objective of this work was to develop nanostructured lipid carriers (NLCs) with preservation effect by using pea protein isolate (PPI) nanoparticles as emulsifiers, candelilla wax (CW) as organo-gelator and d -limonene (DL) as antifungal agent. The optimal formulation parameters of NLCs were firstly determined based on results of particle size, poly-dispersity index and zeta potential, and then NLCs prepared by optimal formulation were further characterized. The results showed that DL was successfully encapsulated inside NLCs. Moreover, the encapsulation of amorphous DL led to more disordered crystalline state of NLCs. In addition, in comparing the properties of NLCs and nanoemulsions (NEs) without CW, it was found that the addition of CW seemed to have several beneficial effects on NLCs: 1) NLC droplets were well dispersed, whereas NE droplets exhibited coalescence and flocculation; 2) compared with NEs, NLCs displayed excellent storage stability and inhibition ability of DL release. Furthermore, antifungal activity of NLCs was observed by in vitro and in vivo study. The acquired information in current research can provide novel insight into development of stable and antifungal nanocarriers that own a promising application in tomato preservation. [Display omitted] • NLCs were produced by pre-emulsification followed by ultrasonic treatment. • Candelilla wax (CW) was presumed to be important for the crystallization of NLCs. • CW endowed NLCs with high physical stability and retention rate of d -limonene. • NLCs showed good inhibition effect on the growth of Botrytis cinerea. [ABSTRACT FROM AUTHOR]

In the current study, silibinin-loaded nanostructured lipid carriers (Sili-NLCs) was synthesized, and the hepatoprotective effectiveness of Sili-NLCs against diazinon (DZN)-induced liver damage in male mice was evaluated. The emulsification-solvent evaporation technique was applied to prepare Sili-NLCs, and characterized by using particle size, zeta potential, entrapment efficacy (EE %), in vitro drug release behavior, and stability studies. In vivo, studies were done on male mice. Hepatotoxicity in male mice were induced by DZN (10 mg/kg/day, i.p.). Four groups treated with silibinin and Sili-NLCs with the same doses (100 and 200 mg/kg, p.o.). On 31th days, serum and liver tissue samples were collected. Alanine (ALT) and aspartate (AST) aminotransferase levels, oxidative stress biomarkers, inflammatory cytokines, and histopathological alterations were assessed. The Sili-NLCs particle size, zeta potential, polydispersity index (PDI), and EE % were obtained at 220.8 ± 0.86 nm, −18.7 ± 0.28 mV, 0.118 ± 0.03, and 71.83 ± 0.15%, respectively. The in vivo studies revealed that DZN significantly increased the serum levels of AST, ALT, hepatic levels of lipid peroxidation (LPO), and tumor necrosis factor-α (TNF-α), while decreased the antioxidant defense system in the mice's liver. However, Sili-NLCs was more effective than silibinin to return the aforementioned ratio toward the normal situation, and these results were well correlated with histopathological findings. Improvement of silibinin protective efficacy and oral bioavailability by using NLCs caused to Sili-NLCs can be superior to free silibinin in ameliorating DZN-induced hepatotoxicity in male mice. [Display omitted] • DZN hepatotoxicity was evaluated by oxidative stress, inflammation, and histopathological studies. • DZN induced oxidative stress, inflammation and hepatic injuries. • SB-NLCs administration decreased lipid peroxidation, TNF-α, and liver damage. • SB-NLCs was more effective than free SB to attenuate hepatotoxicity induced by DZN. [ABSTRACT FROM AUTHOR]

This work aims at (1) assessing the potential of repurposing simvastatin (SV) to support the most common therapies against melanoma and (2) developing an innovative topical adhesive film, composed by chitosan-coated nanostructured lipid carriers (Ch-NLC) used as drug vehicle. A factorial design approach was employed as the basis for the formulation development. Optimized Ch-NLC displayed a particle size of 108 ± 1 nm, a polydispersity index of 0.226, a zeta potential of 17.0 ± 0.6 mV, as well as an entrapment efficiency of 99.86 ± 0.08%, and SV loading of 14.99 ± 0.01%. The performance of SV-Ch-NLC films was assessed in terms of release, permeation, and adhesion, as critical quality attributes. Cutaneous tolerability and in vitro cytotoxicity studies were performed to warrant film safety and drug effectiveness, respectively. The topical films provided a sustained release kinetic profile of SV and were classified as nonirritant systems. The encapsulation of SV increased cytotoxicity in melanoma cells. The key role of squalene as nanostructuring agent of the lipid nanoparticle matrix and as permeation enhancer was highlighted, suggesting its key action for potentiating skin permeation and uptake into melanoma cells. Topical SV-Ch-NLC films are thus able to provide an in situ extended drug delivery and useful as coadjuvant treatment of melanoma skin lesions. [ABSTRACT FROM AUTHOR]

This study was conducted to develop an in situ thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, in vitro permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40 nm, encapsulation efficiency of 89.97%, zeta potential of 12.9 mV, and polydispersity index of 0.31. All the in situ formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1 °C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the in situ gel formulation. The cornea penetration of sertaconazole for the in situ gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis. [ABSTRACT FROM AUTHOR]

The objective of the present investigation was to improve the skin deposition and retention of metronidazole (MTZ) in rosacea therapy by incorporating it into nanostructured lipid carriers (NLCs). The main challenge in this endeavor was the partial hydrophilicity of MTZ, which mandated careful selection of excipients, including solid and liquid lipids, surfactants, and their ratios in combination. NLCs were produced by the phase inversion temperature method and finally converted into a gel for topical application. The prepared nanoparticles were evaluated for their particle size, zeta potential, entrapment efficiency, solid-state characteristics, surface morphology, in vitro drug release, and permeation through excised skin. The gel was additionally characterized for its pH, drug content, viscosity, and spreadability. The prepared nanoparticles were spherical in shape and of size less than 300 nm. Incorporation of judiciously chosen excipients made possible a relatively high entrapment efficiency of almost 40%. The drug release was found to be biphasic, with an initial burst release followed by sustained release up to 8 hours. In comparison to the plain drug gel, which had a tissue deposition of 11.23%, the NLC gel showed a much superior and desirable deposition of 26.41%. The lipophilic nature of the carrier, its size, and property of occlusion enabled greater amounts of drug to enter and be retained in the skin, simultaneously minimizing permeation through the skin, i.e. systemic exposure. The results of the study suggest that NLCs of anti-rosacea drugs have the potential to be used in the therapy of rosacea. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Nanostructured lipid carriers (NLC) are biocompatible and biodegradable nanoscale systems with extensive application for controlled drug release. However, the development of optimal nanosystems along with a reproducible manufacturing process is still challenging. In this study, a two-step experimental design was performed and databases were successfully modelled using Artificial Intelligence techniques as an innovative method to get optimal, reproducible and stable NLC. The initial approach, including a wide range of values for the different variables, was followed by a second set of experiments with variable values in a narrower range, more suited to the characteristics of the system. NLC loaded with rifabutin, a hydrophobic drug model, were produced by hot homogenization and fully characterized in terms of particle size, size distribution, zeta potential, encapsulation efficiency and drug loading. The use of Artificial Intelligence tools has allowed to elucidate the key parameters that modulate each formulation property. Stable nanoparticles with low sizes and polydispersions, negative zeta potentials and high drug loadings were obtained when the proportion of lipid components, drug, surfactants and stirring speed were optimized by FormRules® and INForm®. The successful application of Artificial Intelligence tools on NLC formulation optimization constitutes a pioneer approach in the field of lipid nanoparticles. [ABSTRACT FROM AUTHOR]

In the present study, sulforaphane (SFN)-loaded nanostructured lipid carriers (NLC) were developed and optimized for improved oral efficacy against cancer. The SFN-loaded NLC formulation was developed by melt emulsification ultrasonication technique and optimized by Box-Behnken statistical design. The optimized SFN-loaded NLC formulation composed of precirol® ATO 5 (solid lipid) and vitamin E (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and Tween 80 (1%) as surfactant. The mean particle size, polydispersity index, zeta potential, entrapment efficiency (%) and drug loading (%) of optimized SFN-loaded NLC formulation was observed to be 145.38 ± 4.46 nm, 0.181 ± 0.023, −25.12 ± 2.36 mV, 84.94 ± 3.82% and 14.82 ± 3.46%, respectively. In vitro drug release studies showed that the release of SFN from optimized NLC formulation was significantly higher (86.52 ± 5.48%) compared to SFN suspension (38.47 ± 5.52%) up to 24 h. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the NLC compared to plain SFN solution and were further confirmed by CLSM. MTT assay in different cancer cell lines showed that the optimized SFN-loaded NLC formulation exhibited significantly improved (p < .05) cytotoxicity compared to free SFN solution. SFN-loaded NLC formulation showed significantly improved antioxidant activity compared to free SFN solution. Furthermore, pharmacokinetic study on albino Wistar rats showed 5.04-fold increase in relative oral bioavailability with NLC (p < .05) compared to SFN suspension. Therefore, NLC represents a great potential for improved efficacy of SFN after oral administration. [ABSTRACT FROM AUTHOR]

The global burden of cancer have encouraged oncologists to develop novel strategies for treatment. Present study was proposed to develop Arginyl-glycyl-aspartic acid (RGD)-containing nanostructured lipid carriers (NLC) as a delivery system for improving the anticancer capability of epigallocatechin gallate (EGCG) on breast cancer cell line by attaching to integrin superfamily on cancer cells. For this purpose, RGD-containing EGCG-loaded NLC were prepared by hot homogenization technique and characterized by different techniques. Then, cytotoxic and apoptotic effects of prepared nanoparticles and their uptake into cells was evaluated. As results, the nanoparticles with particle size of 85 nm, zeta potential of −21 mV, encapsulation of 83% were prepared. Cytotoxicity and apoptosis experiments demonstrated that EGCG-loaded NLC-RGD possessed greatest apoptotic activity. Furthermore, it has been shown that, EGCG-loaded NLC-RGD causes cell cycle arresting more effective than EGCG. Therefore, loading EGCG into NLC-RGD make it more effective in both targeting and accumulation into tumour cells, which results from specialized uptake mechanism by adhesion to αvβ3 integrin. The results strengthen our hope that loading EGCG into RGD-containing NLC could possibly overcome the therapeutic limitations of EGCG and make it more effective in cancer therapy. [ABSTRACT FROM AUTHOR]