Rutin-Loaded Nanostructured Lipid Carriers incorporated Hydrogel for the Management Psoriasis: In Vitro and In Vivo Assessment

Nanostructured lipid carriers for targeting drug delivery to the epidermal layer.

Context: For head and neck cancer therapy, co-delivery of two drugs, cisplatin (DDP) plus paclitaxel (PTX), are more effective than single drug therapy. Lipid carriers are promising drug carriers for anti-cancer delivery.Objective: The aim of this study is to construct a folate (FA) decorated nanostructured lipid carriers (NLCs) as nanocarriers for DDP and PTX delivery.Materials and methods: In this study, DDP and PTX were incorporated into NLCs. Folate-PEG-DSPE (FA-PEG-DSPE) was synthesized and decorated the drugs-loaded NLCs (FA-DDP/PTX NLCs). Their average size, zeta potential, drug encapsulation efficiency, drug loading capacity, and in vitro drug release were evaluated. Head and neck cancer cells (FaDu cells) were used for the testing of in vitro cytotoxicity, and in vivo transfection efficiency of NLC was evaluated on mice bearing FaDu cells model.Results: The size of FA-DDP/PTX NLCs was around 127 nm, with a positive zeta potential of 26.7 mV. FA-DDP/PTX NLCs showed the highest cytotoxicity and synergistic effect of two drugs in head and neck cancer cells (FaDu cells) in vitro. The in vivo study revealed the greatest anti-tumor activity than all the other formulations in murine-bearing head and neck cancer model.Discussion and conclusion: FA-DDP/PTX NLCs effectively improves anticancer efficiency for head and neck cancer in vitro and in vivo. The constructed NLCs could be used as a novel carrier to co-delivery DDP and PTX for head and neck cancer therapy.

This study investigates new lipidic nanocarrier preparations for production of babassu oil formulations, which are indicated as less radical herbal therapeutic alternatives for the prevention of benign prostatic hyperplasia. The babassu oil was obtained in high yield using the previously studied, reproducible soxlhet extraction process. We investigated the preparation of nanostructured babassu oil lipid carriers and babassu oil nanoemulsions, to determine conditions that yield a high percentage of babassu oil encapsulation, have appropriate size distribution and zeta potential for vectorization of babassu oil to the prostate. Cytotoxicity tests were performed using intestinal epithelial Caco-2 cells and J-774 macrophages, which indicated that nanostructured lipid carriers for babassu oil are not toxic to front Caco-2 cells and are able to reduce J774 cell viability. This indicates their potential use for treatment against inflammatory processes such as prostatitis and for administration through the oral route. Whereas, in previous studies conducted by our research group, other babassu oil nanosystems showed activity when tested in cell strains of human benign prostatic hyperplasia lineage. The new babassu oil nanostructured lipid carriers prepared in this study can be used as a new prototype for phytotherapic nanoformulations for the prophylaxis of prostate pathologies, since they are highly lipophilic, have narrow size distribution and have low toxicity. Keywords: Benign Prostatic Hyperplasia, lipid nanostructures system, nanoemulsion, nanostructured lipid carriers, Orbignya speciosa oil, phytotherapy, prostatitis. 1.

Objective: The review article highlights the development of nano-formulations like solid lipid nanocarriers and nanostructured lipid carriers and their applicability in different drug delivery systems. Significance: In order to get around some of the drawbacks of traditional formulations, lipid base delivery save received increased interest in recent years. These lipidic carriers are created to get around the drawbacks of other colloidal carriers, including polymeric nanoparticles, emulsions, and liposomes, which have the advantages of great physical stability, a favorable release profile, and tailored drug delivery. Conclusion: Nanostructured lipid carriers are an up-and-coming type of nano-carrier that can be used to develop highly effective and customized treatments for cancer chemotherapy. Changing their surface can help target specific areas and make them work better while lowering the side effects of high doses, which is essential for dealing with drug resistance in cancer chemotherapy.

Objective: This work compares the occlusive effect and the penetration enhancement ability of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), through in vitro skin. Methods: SLN and NLC were prepared by high shear homogenization and characterized by size, polydispersity index, zeta potential, morphology and physical stability. Occlusive effect was assessed by an in vitro test and by measuring TEWL using pig skin. Skin treated with the lipid carriers was visualized by SEM. A penetration test through skin, followed by tape stripping, was carried out using Nile red as a marker. Results: SLN (200 ± 6 nm) and NLC (192 ± 11 nm) were obtained. An occlusion factor of 36% - 39% was observed for both systems, while a reduction in TEWL of 34.3% ± 14.8% and 26.2% ± 6.5% was seen after treatment with SLN and NLC, respectively. SEM images showed a film formed by the lipid carriers, responsible for the occlusion observed. No differences were found between the occlusive effect produced by SLN and NLC in both tests. NLC allowed the penetration of a greater amount of Nile red than SLN: 4.7 ± 1.3 μg and 1.7 ± 0.4 μg, respectively. Conclusion: Both carriers form a film on the skin, providing an occlusive effect with no differences between these two systems. The penetration of a marker (Nile red) into the stratum corneum was quite higher for NLC than for SLN, suggesting an influence of the composition of these particles on their penetration enhancing ability.

Drug delivery technology has a wide spectrum, which is continuously being upgraded at a stupendous speed. Lipid nanocarriers have emerged as a very promising, emerging and rapidly developing tool for the delivery of various drugs lacking solubility, bioavailability and stability in the recent couple of decades. Recent studies show that about 40% of newer drugs have such problems. Initially, a lipid carrier was denoted by the liposome and similar vesicular systems, but currently they are categorized as colloidal nano lipid-based carriers (CNLBC). To avoid the limitation of these CNLBCs in pH- and enzyme-dependent degradation, especially when taken orally or in physical and chemical-related stability issues, newer lipid nanocarriers such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes have shown their importance at greater extent due to low toxicity, improved bioavailability, high biocompatibility, high drug-loading efficiency, protection from degradation in GIT, etc. . Nano structured lipid carriers and SLNs are non-biotoxic since they are biodegradable. Besides, they are highly stable. Their (nano-structured lipid carriers and SLNs) morphology, structural characteristics, ingredients used for preparation, techniques for their production, and characterization using various methods are discussed in this review. Also, although nano-structured lipid carriers and SLNs are based on lipids and surfactants, the effect of these two matrixes to build excipients is also discussed together with their pharmacological significance with novel theranostic approaches, stability and storage. Lipid nanocarriers can load both hydrophilic and lipophilic drug. Solubility is a rate-limiting step in the case of lipophilic drugs (BCS Class II and IV), which can be greatly modified by formulation of lipid nanocarriers. Similarly, lipidic nanocarriers can increase the permeability of most of the hydrophilic drugs (BCS I and III class) which is the rate limiting step this case. These carriers also shows good controlled and target specific drug delivery system which always attracts the attention of researchers.The current chapter aims to present a special concern related to various types of lipid nanocarriers, their detailed description on composition, different methods of preparation, influence of various types of lipids on the different properties of such carriers. It also covers the various physicochemical, formulation, pharmacokinetic, and cytotoxic aspects of such carriers. Furthermore, it includes the marketed formulations of lipid nanocarriers with their company name and trade name.

The first generation of solid lipid carrier systems in nanometer range, Solid Lipid Nanoparticles (SLN), was introduced as an alternative to liposomes. SLN are aqueous colloidal dispersions, the matrix of which comprises of solid biodegradable lipids. SLN are manufactured by techniques like high pressure homogenization, solvent diffusion method etc. They exhibit major advantages such as modulated release, improved bioavailability, protection of chemically labile molecules like retinol, peptides from degradation, cost effective excipients, improved drug incorporation and wide application spectrum. However there are certain limitations associated with SLN, like limited drug loading capacity and drug expulsion during storage, which can be minimized by the next generation of solid lipids, Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure that improves drug loading and firmly incorporates the drug during storage. Owing to their properties and advantages, SLN and NLC may find extensive application in topical drug delivery, oral and parenteral administration of cosmetic and pharmaceutical actives. Cosmeceuticals is emerging as the biggest application target of these carriers. Carrier systems like SLN and NLC were developed with a perspective to meet industrial needs like scale up, qualification and validation, simple technology, low cost etc. This paper reviews present status of SLN and NLC as carrier systems with special emphasis on their application in Cosmeceuticals; it also gives an overview about various manufacturing techniques of SLN and NLC.

Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin

Both pumpkin and kenaf seed oil with carnauba wax (CW) and beeswax (BW) are used to develop nanostructured lipid carriers (NLCs) loaded with Uvinul T150 and Uvinul A Plus Granular for a UV protection formulation. The study aims to optimize the concentration and the type of seed oil in order to develop a stable NLC formulation with high entrapment efficiency, drug loading, antioxidant activities, and UV absorbing properties. The physical properties of the NLCs are analyzed based on the mean particle size, polydispersity index (PDI), long‐term storage stability, Fourier‐transform infrared spectroscopy (FT‐IR), and differential scanning calorimetry (DSC). They are also compared for their entrapment efficiency, drug loading, in vitro antioxidant activities, and in vitro UV absorbing properties. The optimized NLC consists of 10% lipid phase and 1% Uvinul T150 and Uvinul A Plus Granular, respectively. It has mean particle size of 238.20 ± 3.61 nm and remains physically stable on storage at both 25 ± 2 and 40 ± 2 °C. Spherical amorphous NLC structure with encapsulated UV filters is observed by transmission electron microscopy (TEM). Besides, it shows high entrapment efficiency (≥95%) for both Uvinul T150 and Uvinul A Plus Granular in addition to its antioxidant activities as indicated by both DPPH and ABTS radical scavenging activities. In addition, the formulation had high UV absorbing properties, showing its potential to be utilized in the formation of sunscreen prototype.Practical Application: The preliminary study on pumpkin and kenaf seed oil shows bioactive potential with high antioxidant activities. The finding of kenaf seed oil‐NLC can be applied in the cosmetic industry to produce a wide variety of environmental‐friendly products with improved stability and beneficial properties. Also, the application of technology by forming NLCs can be used to develop lotions, creams, etc., with multifunctional properties. Besides, NLCs as carriers for UV filters is proven in the present study to exhibit high entrapment efficiency and drug loading properties. This is beneficial in developing advanced cosmetic prototypes that possess broad spectrum effectiveness with fewer side effects.Nanostructure lipid carriers (NLCs)are applied to encapsulate UV filters with pumpkin and kenaf seed oils. Kenaf seed oil‐NLC (F7) is selected as the best formulation for UV filters encapsulation. With spherical amorphous NLC structure, it shows high entrapment efficiency for the UV filters and antioxidant activities. Results indicate that F7 with high UV absorbing properties remains physically stable upon 12 weeks of storage period.

Development, Characterization, and In Vitro and In Vivo Evaluation of Benzocaine- and Lidocaine-Loaded Nanostructrured Lipid Carriers

The aim of the present study was to formulate and characterize Nano- Structured Lipid Carriers (NLCs) of Febuxostat (FB) incorporated in the gel for the treatment of Gout. FB is a Xanthine Oxidase (XO) inhibitor drug used for chronic Gout and hyperuricemia. FB is a BCS class II drug, therefore, water solubility is very poor, and due to its poor solubility and wettability, it leads to poor dissolution. The hot high-pressure homogenization technique was used in this study to improve the physicochemical property of FB. The carbopol 934 was used to prepare NLCs gel of FB. The NLCs of FB was prepared in different drug: polymer ratios w/w (2:1), (1:1), (1:2), (1:3) and (1:4) with solid lipid (Stearic Acid) and liquid lipid (Oleic acid). The preformulation study of FB included FTIR study melting point, standard calibration curves, and drug-polymer interaction study. The NLCs (1:3) showed high entrapment and drug content. The NLCs gel formulation was 87% released within 6 hours in a controlled manner. NLCs gel modifies the drug release, increases the bioavailability, and reduces side effects of FB. The prepared gel is the efficient formulation for the better treatment of chronic gout and hyperuricemia. The research findings have shown the undesirable side effects associated with the oral route that can be reduced by the use of NLCs formulation through the transdermal route in an effective manner.

The Present investigation is to design, develop and optimize the Nanostructured Lipid Carrier (NLC) containing cardiovascular drug by various independent variables like formulation variables (concentration of phospholipids, surfactants, co-surfactant) and process variables (homogenization time and ultrasonication time). The objective of this research is to choose the suitable and reproducible technique for the formulation of NLC based on dependent variables like Particle Size (PS) in nm, Polydispersity Index (PDI), Zeta potential (ZP) in mV and Entrapment efficiency (EE%) by applying Box Behnken design utilizing - Multiple linear regression method (Design expert 9 software, stat-ease, Inc. USA) and another objective is to prove the enhancement of bioavailability of drug in developed NLC. Comparative invivo pharmacokinetic studies was carried out to determine AUC, Cmax, Tmax , Ke, Vd between drug loaded NLC and commercially available dosage form to prove the enhancement of bioavailability in NLC. From the results obtained, it was concluded that hot homogenization was an optimized technique for the preparation of NLC containing carvedilol and NLC shows better bioavailability when compare to commercial formulation. This data was related to the research project sanctioned by Department of science and technology (DST) entitled “Development of Lipid Nanoparticles Enriched Hydrogels for Transdermal Drug Delivery: Formulation, In vitro Characterization and Pharmacodynamic studies in Animals”

Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s)

The main purpose of this study was to prepare binary lipids-based nanostructured lipid carriers to improve the oral bioavailability of silymarin, a poorly water-soluble liver protectant. Silymarin-loaded nanostructured lipid carriers were prepared by the method of high-pressure homogenization with glycerol distearates (Precirol ATO-5) and oleic acid as the solid and liquid lipids, respectively, and lecithin (Lipoid E 100) and Tween-80 as the emulsifiers. The silymarin-nanostructured lipid carrier prepared under optimum conditions was spherical in shape with mean particle size of ∼78.87 nm, entrapment efficiency of 87.55%, loading capacity of 8.32%, and zeta potential of -65.3 mV, respectively. Invitro release of silymarin-nanostructured lipid carriers was very limited even after 12 h, while invitro lipolysis showed fast digestion of nanostructured lipid carriers within 1 h. Relative oral bioavailability of silymarin-nanostructured lipid carriers in Beagle dogs was 2.54- and 3.10-fold that of marketed Legalon® and silymarin solid dispersion pellets, respectively. It was concluded that nanostructured lipid carriers were potential drug delivery systems to improve the bioavailability of silymarin. Other than improved dissolution, alternative mechanisms such as facilitated absorption as well as lymphatic transport may contribute to bioavailability enhancement.

Lipid based drug delivery system such as Solid lipid nanoparticle (SLN) and Nanostructured lipid carriers (NLC) are among the most promising drug delivery system used in many industries such as food, pharmaceuticals and cosmetics industries. Over the last few years, new constituents of lipids have developed and investigated for enhancement of bioavailability. The present manuscript is an attempt on solving the concerned uncertainty with efficacious peroral administration of hydrophobic drugs through fabricating new lipid formulations, NLC. NLC, the second-generation lipid carrier is usually composed of solid lipids and liquid lipids together in a system. This mixing causes depression in melting point of substrates and converts the mixture into solid form at body temperature and termed as NLC. NLC shows a high drug loading with minimum drug expulsion. The unique advantages of NLC over SLN and Lipid-drug conjugates (LDC) are increased capacity of drug loading, avoidance of drug expulsion. This manuscript gives detailed information on definitions and simple way of production methods, new approaches in formulation of NLC and it also highlights how NLC improves bioavailability of bioactive molecules through peroral route and its future perspective as a pharmaceutical carrier. It also gives idea about the supremacy of NLC over other lipid-based system. Keywords: Bioavailability; Lipids; Lipophilic drugs; Nanostructured lipid carriers; Solid lipid nanoparticle.