A Comprehensive Review on Solid Lipid Nanoparticles as a Carrier for Oral Absorption of Phyto-Bioactives.

Phyto-bioactive (PB) compounds are naturally occurring substances derived from plants that offer significant health benefits ranging from antioxidant and anti-inflammatory activities to potential cancer-fighting properties. However, their widespread application is limited by several inherent limitations, such as low bioavailability, poor biostability, limited aqueous solubility, and no site-specific target. Additionally, the necessity for high concentrations of effective PBs doses further restricts their use. Encapsulating PBs in suitable nanocarriers, particularly solid lipid nanoparticles (SLNs), can enhance their stability in biological environments, improve water solubility, enable controlled release, and allow for targeted delivery. This innovative approach increases bioavailability, reduces toxicity, and potentially lowers effective dosages. The current review examines the critical factors influencing oral PBs delivery, explores how biocompatible and biodegradable SLNs can be optimized to overcome these challenges, and discusses emerging techniques in nanoparticle design that could further enhance the efficacy of PBs delivery systems.

Formulation Optimization and Evaluation of Patented Solid Lipid Nanoparticles of Ambrisentan for Pulmonary Arterial Hypertension.

BACKGROUND: Ambrisentan is a new endothelin receptor antagonist extensively used to manage pulmonary or pulmonary arterial hypertension. OBJECTIVE: The therapeutic efficacy of Ambrisentan is limited due to its reduced solubility, higher log P (3.4), and thus less bioavailability. The recent investigation was concentrated on the improvement of solubility, and bioavailability of Ambrisentan for the therapy of hypertension via solid lipid nanoparticles (SLN) administered orally. METHODS: XRD evaluated the compatibility of Ambrisentan with lipids with FTIR, DSC, and crystalline nature. The SLN was developed by High-pressure homogenization method. The Glyceryl monostearate and Tween 80 indicated the highest solubility, hence selected. The optimization was performed with Box-Behnken Design considering the concentration of GMS (X1), Tween 80 (X2), stirring speed (X3) as independent factors and particle size (Y1), entrapment efficiency (Y2) as dependent factors. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1 and U.S. Patent 2022/0151945A1. RESULTS: The optimized batch F1 showed particle size (130 nm), ZP (-18.9 mV), and entrapment efficiency (85.73 %). The dual release pattern (prompt and sustained) was achieved with the SLNloaded Ambrisentan for about 24 hours. The lyophilized sample was subjected to SEM, which also revealed a spherical shape of a colloidal dispersion with a particle size of 126 nm. Hence, the F1 batch is highly recommended for solid oral delivery and also for the pilot-plant scale-up. CONCLUSION: A marked improvement in the solubility and dissolution of Ambrisentan was attained with the SLN. Moreover, the sustained delivery via the oral route enabled the patient's comfort, compliance, and therapeutic efficacy.

Cytotoxic Impact of Naringenin-Loaded Solid Lipid Nanoparticles on RIN5F Pancreatic ß Cells via Autophagy Blockage.

BACKGROUND: Autophagy plays a crucial role in modulating the proliferation of cancer diseases. However, the application of Naringenin (Nar), a compound with potential benefits against these diseases, has been limited due to its poor solubility and bioavailability. OBJECTIVE: This study aimed to develop solid lipid nanoparticles (Nar-SLNs) loaded with Nar to enhance their therapeutic impact. METHODS: In vitro experiments using Rin-5F cells exposed to Nar and Nar-SLNs were carried out to investigate the protective effects of Nar and its nanoformulation against the pancreatic cancer cell line of Rin-5F. RESULTS: Treatment with Nar and Nar-SLN led to an increase in autophagic markers (Akt, LC3, Beclin1, and ATG genes) and a decrease in the level of miR-21. Both Nar and Nar-SLN treatments inhibited cell proliferation and reduced the expression of autophagic markers. Notably, Nar-SLNs exhibited greater efficacy compared to free Nar. CONCLUSION: These findings suggest that SLNs effectively enhance the cytotoxic impact of Nar, making Nar-SLNs a promising candidate for suppressing or preventing Rin-5F cell growth.

Lipid-based nanoparticles: innovations in ocular drug delivery.

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.

The Science of Solid Lipid Nanoparticles: From Fundamentals to Applications.

Solid lipid nanoparticles (SLNs) play a crucial role in drug delivery, offering benefits such as enhanced bioavailability, targeted distribution, and reduced toxicity. This article provides a comprehensive overview of SLN formulation, development, and advancement in pharmaceutical research, examining their characteristics, classifications, and significance. The review also delves into the real-world applicability of various SLN formulations across different routes of administration, discussing their advantages, disadvantages, and challenges of scalability, along with strategies for efficient implementation. Furthermore, it explores the diverse applications of SLNs through various delivery methods, addressing the obstacles and potential solutions. By highlighting the critical role of SLNs in improving treatment outcomes, this review underscores their importance in modern drug delivery systems.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the delivery of bioactives sourced from plants: part II - applications and preclinical advancements.

INTRODUCTION: Numerous purified bioactive compounds, crude extracts, and essential oils have demonstrated potent antioxidant, antimicrobial, anti-inflammatory, and antiviral properties, particularly in vitro or in silico; however, their in vivo applications are hindered by inadequate absorption and distribution in the organism. The incorporation of these phytochemicals into solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) has demonstrated significant advancements and represents a viable approach to improve their bioavailability through different administration routes. AREAS COVERED: This review discusses the potential applications of SLN and NLC, loading bioactive compounds sourced from plants for the treatment of several diseases. An overview of the preclinical developments on the use of these lipid nanoparticles is also provided as well as the requisites to be launched on the market. EXPERT OPINION: Medicinal plants have gained even more value for the pharmaceutical industries and their customers, leading to many studies exploring their therapeutic potential. Several bioactives derived from plants with antiviral, anticancer, neuroprotective, antioxidant, and antiaging properties have been proposed and loaded into lipid nanoparticles. In vitro and invivo studies corroborate the added value of SLN/NLC to improve the bioavailability of several bioactives. Surface modification to increase their stability and target delivery should be considering.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the delivery of bioactives sourced from plants: part I - composition and production methods.

INTRODUCTION: Nanoparticles (NPs) are widely used in the pharmaceutical field to treat various human disorders. Among these, lipid-based NPs (LNPs), including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are favored for drug/bioactive delivery due to their high stability, biocompatibility, encapsulation efficiency, and sustained/controlled release. These properties make them particularly suitable as carriers of compounds derived from plant sources. AREAS COVERED: This study comprehensively explores updated literature knowledge on SLN and NLC, focusing on their composition and production methods for the specific delivery of drug/bioactive compounds derived from plant sources of interest in pharmaceutical and biomedical fields. EXPERT OPINION: SLN and NLC facilitate the development of more effective natural product-based therapies, aiming to reduce dosage and minimize side effects. These delivery systems align with the consumer demands for safer and more sustainable products, as there are also based on biocompatible and biodegradable raw materials, thereby posing minimal toxicological risks while also meeting regulatory guidelines.

Development, Statistical Optimization, and Characterization of Resveratrol-Containing Solid Lipid Nanoparticles (SLNs) and Determination of the Efficacy in Reducing Neurodegenerative Symptoms Related to Alzheimer's Disease: In Vitro and In Vivo Study.

Resveratrol (RSV), as a natural polyphenol exhibiting antioxidative properties, is studied in the treatment of neurodegenerative diseases. However, RSV has low oral bioavailability. In this study and in order to overcome the issue, RSV was encapsulated into the solid lipid nanoparticles (SLNs). In this study, RSV-loaded solid lipid nanoparticles (RSV-SLNs) were prepared by the solvent emulsification-evaporation technique, and their physicochemical properties were optimized using Box-Behnken response surface methodology. The morphology of the particles was evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The neuroprotective effects of the nanoparticles were investigated in animal models using the Morris water maze (MWM). Then after, the rats were sacrificed, their brains were collected, and the extent of lipid peroxidase (LPO) as well as the level of reduced glutathione (GSH) were determined in the hippocampus section samples. Finally, the collected brain tissues were histologically studied. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), and drug loading (DL%) of the optimized nanoparticles were 104.5 ± 12.3 nm, 0.322 ± 0.11, -3.1 ± 0.15 mV, 72.9 ± 5.31% and 14.6 ± 0.53%, respectively. The microscopic images revealed spherically shaped and nonaggregated nanoparticles. The in vivo studies demonstrated higher efficiency of RSV-SLN in the reduction of escape latency time and improvement in the time spent in the target quadrant compared to free RSV. Moreover, it was demonstrated that RSV-SLN posed a higher potency in the reduction of LPO as well as elevation of the GSH levels in the brain samples. The histological studies revealed a decline in neural degeneration and an improvement in the CA1 pyramidal cell morphology. The obtained data revealed that RSV-SLNs caused more reduction in Alzheimer-related symptoms rather than free RSV.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 µg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

A Review on Ocular Nanoformulation Based Formulations with Highlights on Pediatric Ocular Pharmacokinetics.

The potential use of nanoparticle-based formulations is being explored rapidly for drug delivery in ocular treatment. Despite having several advancements in the area of ocular therapy, the pharmacokinetics-based formulation development for pediatric ocular treatment is still not in proper focus. There are an inadequate number of degenerative ocular ailments with childhood onset. The purpose of this review is to focus on the pharmacokinetics studies of nanoparticle- based formulations for treating ocular diseases and problems associated with the ocular treatment of the pediatric population. Recent studies on pharmaceutical modeling of ocular formulations have also been discussed. Nanoparticle-based formulations were collected by conducting a literature survey on PubMed, Science Direct, and other portals. In this review, we have explored in detail the explanation behind the inequality among available ocular treatment regimens for youngsters as well as adults by specifically focusing on those diseases that can be distressing for children. Latest innovative developments and advancements in drug delivery systems and challenges in their usage particularly for young infant patients were also discussed. It can be concluded that the bioavailability of ocular formulations and their effect on ocular cells can be further enhanced manifolds by the development of nanoparticles-based formulations.

In Vitro Cytotoxicity and Pharmacokinetic Study for Bosutinib Solid Lipid Nanoparticles.

OBJECTIVE: Bosutinib (BST) is a Biopharmaceutics Classification System Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of BST lead to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of BST. Animal data suggest that the absolute bioavailability of BST is about 14-34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid-based drug delivery systems such as solid lipid nanoparticles (SLNs) can be used. METHODS: SLNs are submicron colloidal carriers having a size range of 50-1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. BST can be conveniently loaded into SLNs to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of BST suspension (SUS). RESULTS: An in vitro cytotoxicity study was done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method through ATCC cell lines; the percent inhibition was more in SLN when compared with SUS. The pharmacokinetics of BST-SLNs after oral administration in male Wistar rats was studied. The bioavailability of BST was increased by 2.28 fold when compared with that of a BST SUS. CONCLUSION: The results are indicative of SLNs as suitable lipid-based carrier system for improving the oral bioavailability of BST.

Chondroitin Sulfate for Cartilage Regeneration, Administered Topically Using a Nanostructured Formulation.

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.

Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18-Optimization, Characterization, and Cosmetic Application.

Solid lipid nanoparticles (SLNs) incorporated with retinol and oligopeptide can have a full spectrum of effects on the skin as a compatible combination of ingredients with broad anti-aging properties. The research's main objective was to ensure the stability of lipid nanocarriers containing retinol and peptide due to the planned use of this dispersion as a cosmetic raw material. To confirm the effectiveness of method optimization (high shear homogenization, HSH) and proper selection of substrates, SLN dispersions were obtained in three combinations: 1-non-incorporated SLNs; 2-SLNs containing only retinol; 3-SLNs containing retinol and pentapeptide-18; these were then stored at different temperatures (4, 25, 45 °C) for 4 weeks. The desired values of the physicochemical parameters of the optimized dispersion of lipid nanoparticles incorporated with retinol and oligopeptide over the required storage period were confirmed: mean particle size (Z-Ave) = 134.7 ± 0.3 nm; polydispersity index (PDI) = 0.269 ± 0.017 [-]; zeta potential (ZP) = 42.7 ± 1.2 mV (after 4 weeks at 25 °C). The results confirmed the proper selection of the SLN production method and the effectiveness of the optimization performed. The possibility of using the obtained raw material as an ingredient in cosmetic products with anti-aging properties was indicated.

Lipid-Based Nanocarriers: Bridging Diagnosis and Cancer Therapy.

Theranostics is a growing field that matches diagnostics and therapeutics. In this approach, drugs and techniques are uniquely coupled to diagnose and treat medical conditions synergically or sequentially. By integrating diagnostic and treatment functions in a single platform, the aim of theranostics is to improve precision medicine by tailoring treatments based on real-time information. In this context, lipid-based nanocarriers have attracted great scientific attention due to their biodegradability, biocompatibility, and targeting capabilities. The present review highlights the latest research advances in the field of lipid-based nanocarriers for cancer theranostics, exploring several ways of improving in vivo performance and addressing associated challenges. These nanocarriers have significant potential to create new perspectives in the field of nanomedicine and offer promise for a significant step towards more personalized and precise medicine, reducing side effects and improving clinical outcomes for patients. This review also presents the actual barriers to and the possible challenges in the use of nanoparticles in the theranostic field, such as regulatory hurdles, high costs, and technological integration. Addressing these issues through a multidisciplinary and collaborative approach among institutions could be essential for advancing lipid nanocarriers in the theranostic field. Such collaborations can leverage diverse expertise and resources, fostering innovation and overcoming the complex challenges associated with clinical translation. This approach will be crucial for realizing the full potential of lipid-based nanocarriers in precision medicine.

Lipid-based Non-viral Vector: Promising Approach for Gene Delivery.

OBJECTIVES: The present review aims to discuss various strategies to overcome intracellular and extracellular barriers involved in gene delivery as well as the advantages, challenges, and mechanisms of gene delivery using non-viral vectors. Additionally, patents, clinical studies, and various formulation approaches related to lipid-based carrier systems are discussed. METHODS: Data were searched and collected from Google Scholar, ScienceDirect, Pubmed, and Springer. RESULTS: In this review, we have investigated the advantages of non-viral vectors over viral vectors. The advantage of using non-viral vectors are that they seek more attention in different fields. They play an important role in delivering the genetic materials. However, few nonviral vector-based carrier systems have been found in clinical settings. Challenges are developing more stable, site-specific gene delivery and conducting thorough safety assessments to minimize the undesired effects. CONCLUSION: In comparison to viral vectors, nonviral vector-based lipid nanocarriers have more advantages for gene delivery. Gene therapy research shows promise in addressing health concerns. Lipid-based nanocarriers can overcome intracellular and extracellular barriers, allowing efficient delivery of genetic materials. Non-viral vectors are more attractive due to their biocompatibility, ease of synthesis, and cost-effectiveness. They can deliver various nucleic acids and have improved gene delivery efficacy by avoiding degradation steps. Despite limited clinical use, many patents have been filed for mRNA vaccine delivery using non-viral vectors.

Formulation Strategy and An Overview of Nano-Structured Lipid Carrier-Based Topical Gel as a Novel Drug Delivery System.

Nano-Structured Lipid Carriers (NLCs) are improved Solid Lipid Nanoparticles (SLNs) that recover the permanency and capacity of drug payload. There are 3 different types of NLCs which have been anticipated. The aforementioned Lipid Nano Particles (LNPs) possess possible tenders in drug delivery systems, cosmeceuticals, clinical research and many others. Here, we highlight the structure, ingredients, different manufacturing techniques and analysis of NLCs which are rudiments in formulating a unique drug delivery system. These types of formulations are therapeutically advantageous like skin hydration, occlusion and improved bioavailability as well as skin targeting. In this article, we have also discussed the features, and novelty of NLCs, different advantages as promising assistance in topical drug delivery systems, shortcomings and utilisations of LNPs by concentrating on NLCs.

Solid lipid nanoparticle formulation maximizes membrane-damaging efficiency of antimicrobial nisin Z peptide.

Solid lipid nanoparticles (SLNs) can protect and deliver naturally derived or synthetic biologically active products to target sites in vivo. Here, an SLN formulation produces a measured four-fold reduction in inhibitory concentration of an antimicrobial peptide nisin Z against S. aureus as compared to the free peptide, indicating the successful delivery and enhanced effectiveness of the SLN-encapsulated bacteriocin. Spherical SLNs of size 79.47 ± 2.01 nm and zeta potential of -9.8 ± 0.3 mV were synthesised. The lipid formulation maximizes the membrane-damaging mode of action of the free peptide with more and larger-sized pores formed on bacterial membranes treated with nisin Z SLNs as measured from scanning electron microscopy and transmission electron microscopy. Flow cytometry measurements precisely quantified an enhanced dye leakage from pre-labeled bacterial cells when treated with nisin Z-loaded SLNs compared to free peptide. The lipid formulation accelerated cell death by killing all the cells within half an hour compared to the equivalent concentration of free peptide which was not bactericidal. Molecular dynamics simulations revealed a mechanism of SLN facilitated binding to the lipid II bacterial cell wall precursor via enhanced adsorption of nisin Z at the inner bacterial cell membrane bilayer. These findings confirmed the potential of SLN formulations for the effective delivery of therapeutic peptides for next-generation antibiotics that are active at low concentrations with the potential to mitigate antimicrobial resistance.

A Comparative Mathematical Analysis of Drug Release from Lipid-Based Nanoparticles.

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.

Recent Advances in the Preparation, Properties, and Applications of Solid Lipid Nanoparticles in Drug Delivery.

Solid lipid nanoparticles (SLNs) are one of the extensively utilized nanocarriers in the pharmaceutical field due to their biocompatibility and biodegradability. These features of the carrier system have fuelled its use as the drug delivery system since the last three decades. This review presents different SLN preparation techniques, such as high shear homogenization, hot homogenization, cold homogenization, microemulsion-based technique, etc. The physicochemical nature of SLNs, comprising drug loading, drug release, particle size, zeta potential, stability, cytotoxicity, and cellular uptake, has been concisely discussed. The article also explains why SLNs are preferred to develop drug delivery systems in several pharmaceutical preparations. The key ingredients like lipid, surfactant/ stabilizer accompanied by co-surfactant, cryoprotectant, or charge modifiers used to fabricate SLNs are also briefly conferred. Here is an elaborate discussion of drugs that are used through various routes by the SLN carrier system and their outcome for utilization of this system. Regulatory aspects, patent aspects, and future prospects of SLN are also discussed here.

Design and optimization of chitosan-coated solid lipid nanoparticles containing insulin for improved intestinal permeability using piperine.

The objective of this research was to optimize the composition and performance of chitosan-coated solid lipid nanoparticles carrying insulin (Ch-In-SLNs) and to assess the potential of piperine in enhancing the intestinal permeability of insulin from these SLNs in vitro. The SLNs were formulated from glyceryl behenate (GB), soya lecithin, and poloxamer® 407, and then coated with a combination of chitosan and piperine to facilitate insulin penetration across the gastrointestinal (GI) mucosa. A Box-Behnken Design (BBD) was utilized to optimize the Ch-In-SLNs formulations, with PDI, particle size, zeta potential, and association efficiency (AE) serving as the response variables. The resulting Ch-In-SLNs exhibited excellent monodispersity (PDI = 0.4), optimal particle size (654.43 nm), positive zeta potential (+36.87 mV), and low AE values. The Ch-In-SLNs demonstrated sustained release of insulin for 12 h in simulated gastric fluid (SGF) and intestinal fluid (SIF), with increased release in the latter. After incubation in SGF and SIF for 12 h, the insulin SLNs retained 54 and 41 % of their initial insulin load, respectively, indicating effective protection from gastric enzymes. Permeation studies using goat intestine and Caco-2 cell lines indicated improved insulin permeation in the presence of piperine. Additionally, cell uptake studies confirmed the role of piperine in enhancing insulin permeation.