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Aim: Cancer constitutes the second leading cause of death worldwide, with conventional therapies limited by significant side effects. Melatonin (MEL), a natural compound with antitumoral properties, suffers from instability and low solubility. To overcome these issues, MEL was encapsulated into nanostructured lipid carriers (MEL-NLC) containing rosehip oil to enhance stability and boost its antitumoral activity. Methods: MEL-NLC were optimized by a design of experiments approach and characterized for their physicochemical properties. Stability and biopharmaceutical behavior were assessed, along with interaction studies and in vitro antitumoral efficacy against various cancer cell lines. Results: Optimized MEL-NLC exhibited desirable physicochemical characteristics, including small particle size and sustained MEL release, along with long-term stability. In vitro studies demonstrated that MEL-NLC selectively induced cytotoxicity in several cancer cell lines while sparing healthy cells. Conclusion: MEL-NLC represent a promising alternative for cancer, combining enhanced stability and targeted antitumoral activity, potentially overcoming the limitations of conventional treatments. Plain Language Summary Despite current advances, cancer is the second cause of death worldwide, but conventional therapies have side effects and limited efficacy. Natural therapies are emerging as suitable alternatives and, among them, Melatonin is a well-known compound with antitumoral properties. However, it is degraded by light, decreasing its therapeutical activity. In order to effectively deliver Melatonin into cancer cells, it has been encapsulated into biodegradable nanoparticles containing rosehip oil, which may boost the antitumoral properties. These nanoparticles have been optimized, showing a small size and a high Melatonin encapsulation, sustained drug release and good stability. Furthermore, in vitro studies demonstrated antitumoral activity against several cancer cell lines, also showing a high internalization inside them. Moreover, studies conducted using chicken embryonated eggs, showed that nanoparticles were non-toxic, thus confirming its promising therapeutical applications. Article highlights Melatonin-loaded NLC containing rosehip oil were optimized employing the design of experiments approach. Melatonin-loaded NLC showed suitable physicochemical properties (average size <200 nm, PI <0.2, ZP ≈ -20 mV and encapsulation efficiency ≈80%). Melatonin lipid nanoparticles interaction studies revelated the successful loading of the drug into NLC, with a more amorphous matrix. Melatonin-NLC showed a prolonged release over 48 h, adjusted to a two-phase decay model. Melatonin-loaded NLC demonstrated a long-term stability for more than 1 year. Melatonin-loaded NLC were cytotoxic against tumoral cell lines, being internalized in a fast and sustained manner. [ABSTRACT FROM AUTHOR]

Mathematical modeling of drug release from drug delivery systems is crucial for understanding and optimizing formulations. This research provides a comparative mathematical analysis of drug release from lipid-based nanoparticles. Drug release profiles from various types of lipid nanoparticles, including liposomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nano/micro-emulsions (NEMs/MEMs), were extracted from the literature and used to assess the suitability of eight conventional mathematical release models. For each dataset, several metrics were calculated, including the coefficient of determination (R2), adjusted R2, the number of errors below certain thresholds (5%, 10%, 12%, and 20%), Akaike information criterion (AIC), regression sum square (RSS), regression mean square (RMS), residual sum of square (rSS), and residual mean square (rMS). The Korsmeyer-Peppas model ranked highest among the evaluated models, with the highest adjusted R2 values of 0.95 for NLCs and 0.93 for other liposomal drug delivery systems. The Weibull model ranked second, with adjusted R2 values of 0.92 for liposomal systems, 0.94 for SLNs, and 0.82 for NEMs/MEMs. Thus, these two models appear to be more effective in forecasting and characterizing the release of lipid nanoparticle drugs, potentially making them more suitable for upcoming research endeavors. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to formulate and evaluate nanostructured lipid carriers (NLCs) of the poorly water soluble anticancer drug Flutamide. Methods: Flutamide-loaded NLCs were formulated by the melt-emulsification ultrasonication method using solid lipid (Precirol ATO 5), liquid lipid (Linseed oil) and surfactants (Tween 80 and Koliphor RH 40). Box Behnken design using 3 factors and 3 levels were utilized to study key cause impact relationship between independent and dependent variables. Results: The optimized Flutamide NLCs further evaluated for different parameters. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies showed spherical morphology and smooth texture of Flutamide NLCs. The optimized Flutamide-loaded NLCs showed high encapsulation efficiency of 97.7 ± 4.98%. The in vitro drug release of 88.15 ± 1.16% was shown by optimized Flutamide NLCs and followed Korsemeyer-peppas kinetics with Fickian diffusion as a drug release mechanism. The in vitro cell line studies on PC3 cells showed satisfactory results. Conclusion: NLCs could have great potential to deliver Flutamide by oral route in the treatment and management of prostate cancer by oral route. [ABSTRACT FROM AUTHOR]

The current study aims to prepare agomelatine-loaded nanostructured lipid carriers (AGO-loaded NLCs) and their administration through the intranasal route in an attempt to circumvent hepatic metabolism, facilitate controlled release, and increase cerebral distribution, etc. Agomelatine faces several challenges such as a fast metabolic process, limited solubility, gastrointestinal vulnerability, enzymatic cleavage, and decreased bioavailability. These challenges collectively undermine its therapeutic effectiveness. Therefore, the goal of the current work is to develop agomelatine-loaded NLCs with enhanced drug entrapment, extended release, and improved stability. Agomelatineloaded NLCs were prepared by using Glyceryl monostearate and Neroli oil as solid lipid and liquid lipid respectively, While Tween 80 and poloxamer 188 were used as surfactant and co-surfactant. The technique of melt emulsification ultrasonication was employed to prepare these NLCs. The prepared formulation was optimized utilizing a three-factor, three-level Box-Behnken design with total lipid percentage, surfactant, and co-surfactant percentage, and ultrasonication time as independent variables and particle size, zeta potential, and percentage entrapment efficiency as dependent variables. The optimized NLCs size was found to be 122 ± 3.19 nm and the results from transmission electron microscopy are likewise within this size range (under 150 nm) and showed that the particles were homogeneous and nearly spherical, with porous and irregular surface features. Polydispersity index, zeta potential, entrapment efficiency, and drug release % were observed as 0.353 ± 0.15, -33.7 ± 2.35 mV, 90.57 ± 0.984% and 94.65 ± 2.39% respectively. The findings from the permeation study indicated a substantial enhancement in permeation for AGO-loaded NLCs when compared to AGO solution. [ABSTRACT FROM AUTHOR]

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]

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata. Reversal of alopecia areata with topical TFB NPs treatment by blocking the JAK-STAT signaling pathways, reduced the expression levels of IFN-γ and the frequencies of NKG2D+CD8+ T cells, restored immune environment and promoted hair regrowth. [Display omitted] • Ex vivo mouse hair follicles model was used to assess formulations. • Hair follicles blocked skin model was used to evaluate drug permeation. • Cationic nanostructured carriers minimize systemic circulation and maximize hair follicle targeting. • The formulation restored immune privilege and ensured safe topical delivery for the treatment of alopecia areata. [ABSTRACT FROM AUTHOR]

Skin carcinoma remains one of the most widespread forms of cancer, and its global impact continues to increase. Basal cell carcinoma, melanoma, and squamous cell carcinoma are three kinds of cutaneous carcinomas depending upon occurrence and severity. The invasive nature of skin cancer, the limited effectiveness of current therapy techniques, and constraints to efficient systems for drug delivery are difficulties linked with the treatment of skin carcinoma. In the present era, the delivery of drugs has found a new and exciting horizon in the realm of nanotechnology, which presents inventive solutions to the problems posed by traditional therapeutic procedures for skin cancer management. Lipid-based nanocarriers like solid lipid nanoparticles and nanostructured lipid carriers have attracted a substantial focus in recent years owing to their capability to improve the drug's site-specific delivery, enhancing systemic availability, and thus its effectiveness. Due to their distinct structural and functional characteristics, these nanocarriers can deliver a range of medications, such as peptides, nucleic acids, and chemotherapeutics, via different biological barriers, such as the skin. In this review, an effort was made to present the mechanism of lipid nanocarrier permeation via cancerous skin. In addition, recent research advances in lipid nanocarriers have also been discussed with the help of in vitro cell lines and preclinical studies. Being a nano size, their limitations and toxicity aspects in living systems have also been elaborated. [ABSTRACT FROM AUTHOR]

Abstract 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.

Nasrul Wathoni,1,&ast; Cecep Suhandi,1,&ast; Khaled M Elamin,2,&ast; Ronny Lesmana,3,4,&ast; Nurhasni Hasan,5,&ast; Ahmed Fouad Abdelwahab Mohammed,6,&ast; Ali El-Rayyes,7,&ast; Gofarana Wilar8,&ast; 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; 2Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 862-0973, Japan; 3Physiology Division, Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 4Biological Activity Division, Central Laboratory, Universitas Padjadjaran, Bandung, Indonesia; 5Department of Pharmacy Science and Technology, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, 90245, Indonesia; 6Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; 7Department of Chemistry, College of Science, Northern Border University, Arar, Saudi Arabia; 8Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia&ast;These authors contributed equally to this workCorrespondence: Nasrul Wathoni, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia, Tel +62-22-842-888-888, Email nasrul@unpad.ac.idAbstract: The current treatments for wound healing still exhibit drawbacks due to limited availability at the action sites, susceptibility to degradation, and immediate drug release, all of which are detrimental in chronic conditions. Nano-modification strategies, offering various advantages that can enhance the physicochemical properties of drugs, have been employed in efforts to maximize the efficacy of wound healing medications. Nowadays, nanostructured lipid carriers (NLCs) provide drug delivery capabilities that can safeguard active compounds from environmental influences and enable controlled release profiles. Consequently, NLCs are considered an alternative therapy to address the challenges encountered in wound treatment. This review delves into the application of NLCs in drug delivery for wound healing, encompassing discussions on their composition, preparation methods, and their impact on treatment effectiveness. The modification of drugs into the NLC model can be facilitated using relatively straightforward technologies such as pressure-based processes, emulsification techniques, solvent utilization methods, or phase inversion. Moreover, NLC production with minimal material compositions can accommodate both single and combination drug delivery. Through in vitro, in vivo, and clinical studies, it has been substantiated that NLCs can enhance the therapeutic potential of various drug types in wound healing treatments. NLCs enhance efficacy by reducing the active substance particle size, increasing solubility and bioavailability, and prolonging drug release, ensuring sustained dosage at the wound site for chronic wounds. In summary, NLCs represent an effective nanocarrier system for optimizing the bioavailability of active pharmacological ingredients in the context of wound healing. Keywords: drug delivery, nanocarrier, nanostructured lipid carriers, wound healing

Yi Zhu,1,2,&ast; Meiling Chen,3,&ast; Chuangzan Yang,1,2 Geng Lu,1,2 Sa Huang,1,2 Meili Chen,3 Yufei Wang,4 Junfeng Ban1– 3 1Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, People’s Republic of China; 4Analytical and Testing Center of Guangzhou University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufei Wang; Junfeng Ban, Email yufei_wang@gzhu.edu.cn; banjunfeng@163.comPurpose: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions.Methods: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats.Results: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug’s half-life in vivo.Conclusion: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug’s in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib. Keywords: nanostructured lipid carriers, celecoxib, HPLC-MS/MS, pharmacokinetics

Simple Summary: Simple Summary: Periodontitis is a common disease in dogs. While dental scaling and polishing are effective treatments, they come with drawbacks such as anesthetic risks and high costs. To address these challenges, Alpha-Mangostin and clove oil, known for their antibacterial and anti-inflammatory properties, have been used as alternative treatments. Nanotechnology has revolutionized the field of medicine, offering unprecedented advancements in the diagnosis and treatment of various conditions in both humans and animals. As research and development continue to advance, the potential for nanotechnology to address some of the most challenging medical issues, including antimicrobial resistance, is likely to expand, making it an integral component of modern healthcare. This study represents a pioneering effort in developing a pharmaceutical nanostructured lipid carrier spray loaded with Alpha-Mangostin and clove oil as a therapeutic innovation for periodontitis in dogs. The product displayed bacteriostatic efficacy, surpassing certain antibiotic drugs, and high stability. So, its application is valuable in the field of veterinary dentistry. Nanostructured lipid carriers (NLC) represent the second generation of nanoparticles, offering numerous advantages over conventional delivery systems. These include improved stability, enhanced drug-loading capacity, and controlled release profiles, making them highly attractive candidates for a wide range of therapeutic applications. Their suitability for hydrophobic drugs like a traditional medicinal plant of Thailand as clove oil and alpha-mangostin. We investigated into nanostructured lipid carriers loaded with Alpha-Mangostin and clove oil (NLC-AMCO) into the physicochemical and biological characteristics to identify the formulation with the highest efficacy for treatment. The particle size, charge, polydispersity index, and other characterizations were recorded. The realtime ex vivo penetration was explored using canine gingival tissue. Drug sustained release was assessed by HPLC. Moreover, the antibacterial properties were tested by conventional methods. The NLC-AMCO can be stored at up to 40 °C for 60 days without any alterations in particle characteristics. Gingival tissue penetration and sustained drug release were superior compared to unencapsulated counterparts. It exhibited greater effectiveness in inhibiting bacterial growth than the antibiotics tested, particularly against bacteria from the oral cavities of dogs. Therefore, this alternative treatment approach offers cost-effectiveness and ease of administration for pet owners and reduces discomfort for the animals during restraint. [ABSTRACT FROM AUTHOR]

The main goal of cancer treatment is to ensure that the drug reaches the tumor tissue and to reduce the side effects of the drug. This study was conducted to synthesize a novel nanostructured lipid carrier modified with chitosan-folate to deliver diltiazem to cancer cell lines and to evaluate its anticancer effect. Dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectrometer (FTIR) methods were used to characterize the nanoparticles. The cytotoxicity effect on cancer cell lines variants was measured. Flow cytometry was used for cell cycle analysis, and reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the induction of apoptosis. The inflammatory effects were evaluated by molecular analysis, and the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid, 2,2-Diphenyl-1-picrylhydrazyl, and Ferric reducing antioxidant power methods were used to measure the antioxidant power of the nanoparticles. The results reported the mean of the real and hydrodynamic diameter of the nanoparticles as 87.7 and 249 nm, respectively, and the encapsulation efficiency of diltiazem was reported to be 86.6%. The cytotoxicity results revealed that the breast cancer cells were more sensitive to treatment, with a median concentration of 33.5µg/ml. Additionally, the nanoparticle treatment led to the arrest of cells in the SubG1 phase while increasing the expression of caspases 3 and 9, which indicates the activation of the internal pathway of apoptosis. Additionally, the increase in the expression of interleukins 6 and 10 suggests an effect of the nanoparticles on inflammation. In addition, the ability to inhibit 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid and 2,2-Diphenyl-1-picrylhydrazyl free radicals with an average concentration of 577, which is more significant than 1000 µg/ml, and the ability of the nanoparticles to reduce iron ions confirmed the antioxidant effect of diltiazem-loaded nanostructured lipid carriers. These results suggest that the nanoparticles have an excellent potential to treat breast cancer. [ABSTRACT FROM AUTHOR]

Background: Gemcitabine (GEM), a Biopharmaceutical Classification System (BCS) class-III drug, holds promise for non-small cell lung cancer treatment. Utilizing lipid-based nanoparticles for targeted delivery has proven effective in cancer therapy. Biotin receptors, overexpressed in various solid tumors, offer a specific target for enhanced chemotherapy efficacy while minimizing side effects. Hence, this study aimed to formulate biotin-coated Nanostructured Lipid Carriers (NLCs) with Gemcitabine can be delivered to specific tumors by electrostatic attraction. Materials and Methods: Nanostructured Lipid Carrier loaded Gemcitabine was formulated using Oleic acid and Glyceryl monostearate as lipids, with Tetronic 1107 as the surfactant. Formulations were optimized using a 2-factor, 3-level full factorial design approach with Design Expert software. Size of particle, Zeta potential, Polydispersity index, Encapsulation efficiency, Scanning Electron Microscopy, phase contrast microscopy, drug release and in vitro cytotoxicity against A549 cells were assessed for characterization. Results: The optimized Gemcitabine-loaded Nanostructured Lipid Carrier formulation exhibited a particle diameter of 194.5 nanometer (nm) and Biotin-Gemcitabine-Nanostructured Lipid Carrier showed a size of 203.1 nanometer. In vitro drug release efficiency of about 95.125% during 8 hr for Gemcitabine-Nanostructured Lipid Carrier and 96.04% during 24 hr for Biotin-Gemcitabine-Nanostructured Lipid Carrier, suggesting prolonged circulation for the latter. Cytotoxicity assays revealed significant reduction in cell viability and induction of cytotoxic activity Gemcitabine-loaded Nanostructured Lipid Carrier-biotin at low concentrations in A549 cells. Conclusion: The developed biotin coated Nanostructured Lipid Carrier present a promising strategy for targeted delivery of Gemcitabine to Non-Small Cell Lung Cancer (NSCLC). These nanocarriers could provide a targeted and efficient delivery platform to tumor cells. Further in vivo investigations are warranted to validate their safety and therapeutic effectiveness. [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]

The Hibiscus sabdariffa (H. sabdariffa) belongs to the Malvaceae family, and originates from Africa. It is characterized by a high polyphenols content (e.g., quercetin and anthocyanins), and has recognized bioactivity, that makes this plant an interesting resource for possible addition of its extracts to dairy beverages and obtain functional beverages. Nonetheless, it may be observed that many of these phenolic compounds are not stable depending on the environmental conditions. In this work, we propose the use of nanostructured lipid carriers (NLC) as a carrier for the loading of H. sabdariffa extracts, for further incorporation in daily beverages. Polyphenols-enriched extracts from H. sabdariffa were obtained using two distinct extraction approaches: by (i) microwave-assisted extraction (MAE), or by (ii) pressurized liquid extraction (PLE). The obtained extracts were then loaded into NLC to obtain two distinct samples identified as: HS-MAE-NLC and HS-PLE-NLC. The developed nanoparticles were then incorporated into a dairy beverage for the production of fortified milks identified with the same names. The long-term stability, texture properties and in vitro release profile were evaluated. The results show that the fortified milks, HS-MAE-NLC and HS-PLE-NLC, were stable under stress conditions attributed to the enhanced stability provided by the protein content present in the milk. The in vitro release profile of quercetin and anthocyanins from NLC-enriched dairy beverage was more prolonged than the milk containing the non-loaded extract, fitting better to the Korsmeyers–Peppas model. From our results, NLC may be considered a potential approach to formulate photoprotective, anti-inflammatory, and antioxidant bioactives from H. sabdariffa adding the extracts into dairy beverages to increase their bioavailability, and bioactivity. [ABSTRACT FROM AUTHOR]

Background: The therapeutic efficacy of an active Pharmaceutical ingredient depends on its solubility in body fluids. The low bioavailability of nearly 90% of new active Pharmaceutical ingredients and 40% of the existing molecules is attributed to their poor solubility. The current study aimed to improve the oral bioavailability of lapatinib by designing and optimizing nanostructured lipid carriers for it. Materials and Methods: The formulation utilized the microemulsion technique as a method of preparation and the Box Behnken design was used for optimization. Results: The average particle size, drug entrapment, and release, in percentages, were observed to be 237.09 nm, 72.32%, and 74.66% respectively. Conclusion: In vitro studies proved that NSLC significantly releases a drug more than the marketed formulation. [ABSTRACT FROM AUTHOR]

In this study, a functional nanostructured lipid carriers (NLCs)-based hydrogel was developed to repair the damaged epidermal skin barrier. NLCs were prepared via a high-energy approach, using argan oil and beeswax as liquid and solid lipids, respectively, and were loaded with ceramides and cholesterol at a physiologically relevant ratio, acting as structural and functional compounds. Employing a series of surfactants and optimizing the preparation conditions, NLCs of 215.5 ± 0.9 nm in size and a negative zeta potential of −42.7 ± 0.9 were obtained, showing acceptable physical and microbial stability. Solid state characterization by differential scanning calorimetry and X-ray powder diffraction revealed the formation of imperfect crystal NLC-type. The optimized NLC dispersion was loaded into the gel based on sodium hyaluronate and xanthan gum. The gels obtained presented a shear thinning and thixotropic behavior, which is suitable for dermal application. Incorporating NLCs enhanced the rheological, viscoelastic, and textural properties of the gel formed while retaining the suitable spreadability required for comfortable application and patient compliance. The NLC-loaded gel presented a noticeable occlusion effect in vitro. It provided 2.8-fold higher skin hydration levels on the ex vivo porcine ear model than the NLC-free gel, showing a potential to repair the damaged epidermal barrier and nourish the skin actively. [ABSTRACT FROM AUTHOR]

Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box–Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained ex vivo release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. In vivo pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (Cmax = 16.77 µg/g, tmax = 30 min) after intranasal administration compared to intravenous administration (Cmax = 2.53 µg/g, tmax = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain via olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders. [ABSTRACT FROM AUTHOR]

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson's disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD. [ABSTRACT FROM AUTHOR]

Lawsone, a naphthoquinone phytochemical compound present in the plants such as henna, was found to increase the healing process. However, clinical applications are impeded owing to the poor water solubility, low bioavailability, and dyeing property to the hair and skin. Nanostructured lipid carriers (NLCs) are appropriate carriers that cover undesirable effects of drugs, afford sustained release over a prolonged period of time, reduce systematic effects, decrease irritation, and increase tolerance. In this research, a formulation of lawsone incorporated NLC was prepared, and characterized for pharmaceutical application. The synthesized formulation was characterized using electron microscopy, polydispersity index, and zeta potential, and entrapment efficiency and malondialdehyde (MDA) level were evaluated. In order to assess wound healing potential, the wound area was measured at different times post-treatment, showing a structured tissue with better healing signs in NLC- Lw- Lv group in comparison with alpha ointment. NLC- Lw- Lv (NLC containing lawsone and lavender) formulation with mean size of 165.3 ± 4.2 nm, polydispersity index of 0.211, zeta potential of − 24.3 mV, and entrapment efficiency of 79.3 ± 2.9 was subjected to further experiments as optimized formulation. The ex vivo evaluation of formulation in mouse skin indicated better retention, less residue, and permeation in comparison with alpha ointment as standard. MDA level, as the indicator of lipid peroxidation, was lower in the NLC- Lw- Lv treated group. Histological score of microscopic wound healing parameters, such as swelling, re-epithelialization, formation of fibrotic tissue, and granulation, presented significantly better wound contraction in NLC- Lw- Lv treated group. In conclusion, our results propose the effective wound healing ability of lawsone, proved by more effective and an earlier stimulation of wound contraction. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop nano-structured lipid carriers (NLCs) loaded with propolis which is a natural antifungal agent with a pronounced activity against resistant fungal strains as Candida albicans which is the primary cause of vulvovaginal candidiasis (VVC), one of the common vaginitis that affects over 75% of females. In this study, NLCs carrying propolis within their framework were developed for bioavailability enhancement. Such systems were assessed through the examination of their entrapment efficiency (EE), release behaviour, physicochemical assessments, and transmission electron microscopy. High EE (above 95%) and homogeneity were observed in the systems; polydispersity index (PDI) values < 1. Additionally, they exhibited sustained release behaviour for up to 24 h with nano-sized particle size. Propolis NLCs (P1) showed efficient antioxidant activity as well as in vitro antifungal activity against fluconazole-resistant Candida albicans. Moreover, P1 showed a remarkable advantage in depositing propolis in the vaginal tissues and the in vivo study demonstrated that P1 significantly reduced the microbial viable count of Candida albicans after 3 days in the vaginal secretions of the group treated with the nano-formula in compare to the free drug group, with a significant alleviation of the reduced catalase activity in addition to the modulation of tumour necrosis factor-alpha (TNF-α) secretion and downregulation of cyclooxygenase-2 (COX-2) expression in a manner that was dose dependent. Additionally, normal histological structure of the vaginal tissue was observed in the nano-formula treated groups. In conclusion, this novel propolis NLC (P1) showed pronounced efficacy as antifungal/antioxidant therapeutic vehicles. [ABSTRACT FROM AUTHOR]

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo. Graphical abstract Summary points In this study, we developed and characterized nanostructured lipid carriers (NLCs) loaded with mebendazole (MBZ; NLC-MBZ). NLC-MBZ was prepared to investigate its in vitro and in vivo anticancer effects. NLC-MBZ was explored for its inhibitory impact on RanGTP and its potential as an antimetastatic agent in mouse models. NLC-MBZ displayed a size of 155 ± 20 nm with a -27 ± 0.5-mV charge and 90.7% encapsulation efficiency. After 48 h of exposure, the IC50 for free MBZ and NLC-MBZ was 610 and 305 nM, respectively, against MDA-MB-231 breast cancer cell lines. Moreover, NLC-MBZ reduced the size of the primary tumor and inhibited the development of lung metastases. NLC-MBZ reduced the expression CDC25A, SKP2, RbX1 and Cullin1 while increasing the expression of Rb proteins. NLC-MBZ showed antiangiogenic potential that resulted in a reduced rate of lung metastasis in vivo. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Resveratrol (R) is an antioxidant that helps several aspects of aging skin. However, it is slightly soluble in water and unstable under light exposure, necessitating the use of suitable formulations for improved clinical efficacy. Therefore, this study aimed to prepare R-loaded lipid-based nanocarriers for topical delivery, i.e., nanostructured lipid carriers (NLCs) and nanoemulsions (NEs). R-loaded nanocarrier gels were further prepared to increase R loading. The comparative physical properties and antioxidant activity of nanocarriers were performed in terms of particle size, zeta potential, morphology, rheology, R content, in vitro release, antioxidant activity, cytotoxicity and stability. The results revealed that R was successfully loaded into NLCs and NE gels (NEGs), having different physical properties and antioxidant activity depending on the composition of lipid-based nanocarriers. R could be incorporated into NEs and the aqueous gelling phase, resulting in higher R loading. Furthermore, the gelling network was responsible for pseudoplastic flow behavior. The cumulative amount of R released from NEGs was significantly higher than that from NLCs due to the co-surfactant-like properties of NEGs, which resulted in smaller particle sizes. However, NLCs exhibited significantly more antioxidant activity and less cytotoxicity compared to NEGs. The stability of both nanosystems showed no significant change when stored at refrigerator temperature for over 3 months. In conclusion, the various compositions of lipid-based nanocarriers produced a range of physical properties and antioxidant activity. Nonetheless, these NLCs and NEGs have the potential to be nanocarriers for R, which has antioxidant properties for topical application.

Delivery and formulation of oral peptide and protein therapeutics have always been a challenge for the pharmaceutical industry. The oral bioavailability of peptide and protein therapeutics mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of peptide and protein therapeutics focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system (DDS). Nevertheless, undesired physicochemical features of peptide and protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.

Abstract Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way.

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.

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]

Clozapine (CLZ), a tricyclic dibenzodiazepine antipsychotic drug employed for the treatment of Schizophrenia. However, CLZ's significant first-pass effect, poor water solubility, and low oral bioavailability (27%) limit its potential for therapeutic use. The present investigation aimed to prepare CLZ-loaded nanostructured lipid carriers (NLCs) to improve its solubility, bioavailability, and therapeutic efficacy. The NLCs were prepared using an ultrasonic probe sonication technique using selected solid lipids (Gelucire 44/14), liquid lipids (Labrafil M 1944), and surfactants (Monoemul 80). A central composite design approach was adopted to optimize the NLCs. The optimized CLZ-loaded NLCs were evaluated in terms of particle size, zeta potential, surface morphology, crystallinity, drug loading, and in-vitro CLZ release studies. The optimized CLZ-loaded NLCs showed a particle size, zeta potential, and entrapment efficiency of 115.1 ± 2.48 nm, −17 mV and 96.74 ±1.82%, respectively. The morphology revealed the coarsely spherical shape of NLCs. Fourier transform infrared spectroscopy indicated the physical interaction between the CLZ and lipids rather than chemical interaction. The results of powder X-ray diffraction and differential scanning calorimetry showed the conversion of crystalline to amorphous form of CLZ and distributed molecular level in lipid matrix. In the in-vitro release study, pure CLZ showed 14±1.86% release, whereas CLZ-loaded NLC showed initial burst release (20.0±0.56%) followed by sustained release (69.0±1.03%) up to 24 hours. Collectively, results revealed that the developed novel CLZ-loaded NLCs could be a potential formulation to improve efficacy by increasing solubility and prolonging CLZ release and bioavailability with enhanced patient compliance and reduced side effects. [ABSTRACT FROM AUTHOR]

Over the last few decades, cancer has been considered a clinical challenge, being among the leading causes of mortality all over the world. Although many treatment approaches have been developed for cancer, chemotherapy is still the most utilized in the clinical setting. However, the available chemotherapeutics-based treatments have several caveats including their lack of specificity, adverse effects as well as cancer relapse and metastasis which mainly explains the low survival rate of patients. Lipid nanoparticles (LNPs) have been utilized as promising nanocarrier systems for chemotherapeutics to overcome the challenges of the currently applied therapeutic strategies for cancer treatment. Loading chemotherapeutic agent(s) into LNPs improves drug delivery at different aspects including specific targeting of tumours, and enhancing the bioavailability of drugs at the tumour site through selective release of their payload, thus reducing their undesired side effects on healthy cells. This review article delineates an overview of the clinical challenges in many cancer treatments as well as depicts the role of LNPs in achieving optimal therapeutic outcomes. Moreover, the review contains a comprehensive description of the many LNPs categories used as nanocarriers in cancer treatment to date, as well as the potential of LNPs for future applications in other areas of medicine and research. [ABSTRACT FROM AUTHOR]

The main objective of the experiment is to develop and evaluate hydrogel-bearing nanostructured lipid carriers (NLCs) loaded with ketoconazole (KTZ) for the effective treatment of candidiasis. The eugenol was used as a liquid lipid (excipient) for the development of KTZ-loaded NLCs and was explored for anti-fungal effect. The production of NLCs involves high energy processes to generate spherical, uniform particles, having a higher percentage of entrapment efficiency (%EE) for KTZ with 89.83 ± 2.31 %. The data from differential scanning calorimeter (DSC), powder x-ray diffraction (PXRD), and attenuated total reflectance (ATR) demonstrated the KTZ dispersion in NLCs. The NLCs loaded hydrogel possessed optimum spreadability and exhibited shear thinning behavior, indicating the ease of application of the final formulation. The 6.41-fold higher transdermal flux (Jss) was governed for KTZ from KTZ-NLC than coarse-KTZ, which explains the usefulness of NLCs. The KTZ-NLCs exhibited significant 2.58 and 6.35-fold higher retention in the stratum corneum and viable epidermis of the skin. The cell cytotoxicity studies using human dermal fibroblast cell (HDFS) lines depicted the usefulness of NLCs in reducing cell toxicities for KTZ. The KTZ-NLCs were found to inhibit planktonic growth and hyphal transition and showed a larger zone of inhibition against C. albicans strains with a MIC-50 value of 0.39 μg/mL. The antibiofilm activity of KTZ-NLCs at lower concentrations, in contrast to plain KTZ, explained the interaction of developed NLCs with fungal membranes. The overall results depicted the effectiveness of the loading KTZ in the lipid matrix to achieve antifungal activity against C. albicans. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The primary goal of this study was to develop and validate an LC-MS/MS method for the detection of dapagliflozin in nanostructured lipid carriers (NLC) using ion-interaction chromatography. The reversed-phase InfinityLab Poroshell 120 (150 × 4.6 mm, 4 µm) column, using a mobile phase of acetonitrile-25 mM ammonium acetate solution with pH 4.1 (35:65, v/v), effectively separated the analytes and their internal standards. This method has been thoroughly tested and validated to ensure accurate and reliable results. To improve sensitivity and selectivity, mass spectrometry was used in polarity switching mode. In order to study ion transitions for dapagliflozin in both positive and negative mode, multiple reaction monitoring mode was utilized, with the ion transitions being m/z 467.1 [M+CH3COO]-/329.1. The assay's linear calibration range for dapagliflozin was established from 0.05-150 ng/mL to improve drug pharmacokinetics assessment. The analyte's limit of detection (LOD) and limit of quantitation (LOQ) were 0.07 and 0.35 ng/mL, respectively. After testing, no interference was observed in plasma matrices from different sources, including haemolysed and lipemic plasma. The impact of Dapagliflozin-loaded NLC on plasma levels were investigated using this method. [ABSTRACT FROM AUTHOR]

Psoriasis is a complex and persistent autoimmune skin disease. The present research focused on the therapeutic evaluation of betulin-loaded nanostructured lipid carriers (BE-NLCs) towards managing psoriasis. The BE-NLCs were synthesized using the emulsification cum solidification method, exhibiting a spherical shape with a particle size of 183.5±1.82nm and a narrow size distribution window (PDI: 0.142±0.05). A high zeta potential -38.64±0.05mV signifies the relative stability of the nano-dispersion system. BE-NLCs show a drug loading and entrapment efficiency of 47.35±3.25% and 87.8±7.86%, respectively. In vitro release study, BE NLCs show a cumulative percentage release of 90.667±5.507% over BE-sol (57.334±5.03%) and BD-oint (42±4.58%) for 720min. In an ex vivo 24-h permeation study, % cumulative amount permeated per cm2 was found to be 55.667±3.33% from BE-NLCs and 32.012±3.26% from BE-sol, demonstrating a better permeability of 21.66% when compared to the standard formulation BD-oint. The in vivo anti-psoriatic activity in the IMQ-induced model shows topical application of BE-sol, BE-NLCs, and BD-oint resulted in recovery rates of 56%, 82%, and 65%, respectively, based on PASI (Psoriasis Area and Severity Index) score. Notably, BE-NLCs demonstrated a more significant reduction in spleen mass, indicating attenuation of the local innate immune system in psoriatic mice. Reductions in TNF-α, IL-6, and IL-17 levels were observed in both BE-sol and BE-NLCs groups compared to the disease control (DC) group, with BE-NLCs exhibiting superior outcomes (74.05%, 44.76%, and 49.26% reduction, respectively). Soy lecithin and squalene-based NLCs could be better carrier system for the improvement of the therapeutic potential of BE towards management of psoriasis. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most severe lethal malignancies, with approximately 1.6 million deaths every year. Lung cancer can be broadly categorised into small and non-small-cell lung cancer. The traditional chemotherapy is nonspecific, destroys healthy cells and produces systemic toxicity; targeted inhalation drug delivery in conjunction with nanoformulations has piqued interest as an approach for improving chemotherapeutic drug activity in the treatment of lung cancer. Our aim is to discuss the impact of polymer and lipid-based nanocarriers (polymeric nanoparticles, liposomes, niosomes, nanostructured lipid carriers, etc.) to treat lung cancer via the inhalational route of drug administration. This review also highlights the clinical studies, patent reports and latest investigations related to lung cancer treatment through the pulmonary route. In accordance with the PRISMA guideline, a systematic literature search was carried out for published works between 2005 and 2023. The keywords used were lung cancer, pulmonary delivery, inhalational drug delivery, liposomes in lung cancer, nanotechnology in lung cancer, etc. Several articles were searched, screened, reviewed and included. The analysis demonstrated the potential of polymer and lipid-based nanocarriers to improve the entrapment of drugs, sustained release, enhanced permeability, targeted drug delivery and retention impact in lung tissues. Patents and clinical observations further strengthen the translational potential of these carrier systems for human use in lung cancer. This systematic review demonstrated the potential of pulmonary (inhalational) drug delivery approaches based on nanocarriers for lung cancer therapy. [ABSTRACT FROM AUTHOR]

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

Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases like HIV/AIDS. Etravirine is one of the key components of highly active antiretroviral therapy used for the treatment of HIV-1 infections. The aim of the present study was to formulate and evaluate nanostructured lipid carriers of etravirine, intended for targeted delivery to macrophages, using solvent emulsification - evaporation technique. Estimates of drug solubility were employed for selection of solid lipids, liquid lipids and stabilizers for the preparation of NLCs. Design of experiments was used to optimize the formulation with respect to drug-lipid ratio and concentration of stabilizer in the external phase using 32 full factorial design. Particle size of the carriers and drug release characteristics were the responses which were set to suitable levels for optimization. The optimized formulation was prepared and characterized for size, poly dispersity index, zeta potential, entrapment efficiency and appearance. The nanostructured lipid carriers of etravirine were prepared using stearylamine and glyceryl monostearate as solid lipids, Capryol 90 as liquid lipid and polyvinyl pyrrolidone as stabilizer. All experimental batches showed high drug loading efficiencies nearing 99%, indicating that etravirine remained closely associated with the lipids. The nanostructured lipid carriers displayed a zeta potential of -10.1 mv and a particle size of 261.6 nm with a polydispersity index of 0.374. In vitro release of etravirine from the optimized formulation at 2 h was 9% indicative of a low burst; and 56% of the entrapped drug was released after 24 h, suggesting prolonged release characteristics. Thus, etravirine loaded lipidic nanoparticles with potential for targeting cellular reservoirs of the AIDS virus such as macrophages were successfully developed. [ABSTRACT FROM AUTHOR]

Background and purpose: Hair loss is a prevalent problem affecting millions of people worldwide, necessitating innovative and efficient regrowth approaches. Nanostructured lipid carriers (NLCs) have become a hopeful option for transporting bioactive substances to hair follicles because of their compatibility with the body and capability to improve drug absorption. Review approach: Recently, surface modification techniques have been used to enhance hair regeneration by improving the customization of NLCs. These techniques involve applying polymers, incorporating targeting molecules, and modifying the surface charge. Key results: The conversation focuses on how these techniques enhance stability, compatibility with the body, and precise delivery to hair follicles within NLCs. Moreover, it explains how surface-modified NLCs can improve the bioavailability of hair growth-promoting agents like minoxidil and finasteride. Furthermore, information on how surface-modified NLCs interact with hair follicles is given, uncovering their possible uses in treating hair loss conditions. Conclusion: This review discusses the potential of altering the surface of NLCs to customize them for enhanced hair growth. It offers important information for upcoming studies on hair growth.

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 C18 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 (tR) 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.

Curcumin (CUR) is a naturally occurring compound in food known for its potential pharmacological activity but faces challenges due to its high metabolism. Piperine (PIP) is an effective inhibitor of metabolizing enzymes, enhancing the bioavailability of CUR. This work evaluated the lymphatic absorption and ex-vivo intestinal permeability of nanostructured lipid carriers (NLCs) containing PIP and CUR (CP NLCs). The optimized lipid formulation underwent in-vitrodrug release, ex-vivo permeation, and lymphatic uptake studies utilizing chicken intestinal (jejunum) segments. Studies were conducted under different conditions, specifically in the presence and absence of the lymphatic uptake blocker Pluronic-F68 (PF68). PF68 is a non-ionic surfactant commonly used in pharmaceutical research, and it's known for its ability to inhibit lymphatic uptake. In-vitro drug release profiles indicated the controlled release of CUR and PIP from NLCs over 24 h. The ex-vivo permeability study demonstrated that CP NLCs exhibited higher permeation compared to CUR and PIP Suspension (CP Suspension). Studies on the lymphatic uptake of CP NLCs, conducted with and without the presence of the lymphatic uptake blocker PF68, demonstrated a decrease in drug permeation. However, in the absence of the lymphatic blocker, drug transport via the lymphatic path increased significantly by 4.07-fold for CUR and 6.56-fold for PIP. This means that the NLCs significantly enhanced the lymphatic transport of both CUR and PIP. The results imply that the lipid-based NLC system shows potential as a drug delivery method, improving solubility, and aiding in the lymphatic transport of both CUR and PIP.