Nanostructured Lipid Carriers Gel Research Articles

Topical delivery of Bruton’s tyrosine kinase inhibitor and curcumin-loaded nanostructured lipid carrier gel: Repurposing strategy for the psoriasis management

This work investigates the synergistic potential of the nanostructured lipid carrier (NLC) gel of Ibrutinib with Curcumin as a repurposing strategy to treat psoriasis. In the present work, various components such as liquid lipid, solid lipid, and surfactant were selected and optimized based on the solubility of each drug, size, and polydispersity index. The optimized NLC consists of Capryol PGMC as liquid lipid, Glyceryl Mono Stearate as solid lipid, and Pluronics-F-127 as a surfactant. The prepared NLCs have a particle size of 95.12 ± 3.39 nm with PDI of 0.285 ± 0.009, exhibiting high entrapment efficiency (86.04 ± 2.86% for IBR and 87.25 ± 2.14% for CUR) with spherical geometry. CI value of 0.283 suggests synergism. Carbopol 940 was used as a gelling agent and has shown improved flux compared to plain drug gel. Anti-psoriatic studies in BALB/c mice indicated negligible skin irritation and improved histopathological features of psoriasis. Moreover, a reduced amount of inflammatory markers (TNF-alpha, IL-6, IL-22, and IL-23), and psoriasis severity score was observed with prepared gel than the IMQ group. The study suggested integrated benefits of repurposing Ibrutinib with Curcumin as NLC topical gel and it could possibly reduce remission of Psoriasis like inflammation and merit additional investigation.

Zerumbone-Loaded Nanostructured Lipid Carrier Gel Enhances Wound Healing in Diabetic Rats.

This study investigated the healing effects of topical application of zerumbone, a well-known anti-inflammatory compounds loaded on nanostructured lipid carrier gel (Carbopol 940) (ZER-NLCG) on excisional wounds in streptozotocin-induced diabetic rats. Diabetic rats with inflicted superficial skin wound were topically treated with ZER-NLCG, empty NLCG, and silver sulfadiazine cream (SSDC) once daily for 21 days. Wound tissue samples were analyzed for proinflammatory cytokines, namely, interleukin-6 (IL-6), interleukin-1 β (IL-1β), and tumor necrosis factor-α (TNF-α), hydroxyproline contents, catalase, superoxide dismutase activities, and lipid peroxidation level, and were subjected to histopathological analysis, respectively. Among the treated groups, ZER-NLCG was the most effective at decreasing proinflammatory cytokine level and inflammatory cell infiltration while increasing antioxidant enzyme activities, hydroxyproline content, and granulation of wound tissues of diabetic rats. ZER-NLCG is a potent formulation for the enhancement of wound healing in diabetic rats through its anti-inflammatory, antioxidant, and tissue repair activities.

Formulation and Characterization of Febuxostat Loaded Nanostructured Lipid Carriers (NLCs) - Gel for Topical Treatment of Gout.

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.

Design and pharmacodynamic evaluation of DPK-060 loaded Nanostructured lipid carrier embedded gel for dermal delivery: A novel approach in the treatment of atopic dermatitis

DPK-060 is a synthetic, 17 amino acid peptide, structurally derived from the human protein kininogen. DPK-060 mainly acts by membrane disruption mechanism, thus demonstrating strong broad-spectrum antimicrobial activity against both gram-positive and gram-negative microbes, including methicillin-resistant S. aureus (MRSA) in-vitro and in-vivo. Apart from its antimicrobial effect, DPK-060 also possesses anti-inflammatory activity. In addition, DPK-060 has demonstrated positive results in phase II clinical trials in atopic dermatitis (AD) patients; but was not statistically conclusive due to the instability of DPK-060 as a drug substance in the formulation. Thus, the present investigation was aimed to assess and compare the efficacy of DPK-060 nanostructured lipid (NLC) based gel with conventional formulations (free DPK-060 gel and lotion) in AD mice animal models. DPK-060 loaded NLCs were formulated by meltemulsification technique and loaded into Carbopol 934 P gel and characterized for various physicochemical parameters such as particle size, zeta-potential, shape and surface morphology, rheological parameters, in-vitro drug release, cytotoxicity, cellular uptake, ex-vivo skin permeation/deposition, in-vitro antimicrobial activity, and proteolytic stability studies. NLCs exhibited 85 % encapsulation with 6.7 % loading efficacy, a size, and zeta potential of 128.6 nm and −22.5 mv, respectively. Additionally, DPK-060 NLC gel demonstrated controlled release and a better permeation profile in comparison to free DPK-060 gel and lotion. A substantial reduction in pro-inflammatory cytokines levels and improvement in AD lesions was achieved by DPK-060 NLC gel compared to free DPK-060 gel and lotion-based formulations. The present study confirms that DPK-060 NLC gel-based formulation can be an effective, safe, and novel alternative for the treatment of AD.

Development and characterization of griseofulvin loaded nanostructured lipid carrier gel for treating dermatophytosis

The present investigations were aimed at formulating topical gel containing nanostructured lipid carriers (NLCs) of griseofulvin and assess its effectiveness on superficial infections. The drug solubility studies were executed using various lipids and surfactants like Glyceryl monostearate, Oleic acid, Pluronic F 68, and Tween 80, and the concentrations of lipids, surfactants, and emulsifier were optimized using Box-Behnken design (BBD). Microemulsions were made utilizing sonication. The prepared batches (F1 to F15) were analyzed and observed that the optimized batch (F12), containing 0.2% w/w drug, 2% GMS, 2% Pluronic F68 and Tween 80 (in the ratio of 1:1) showed a particle size of 209 nm, zeta potential of -44.12 mV, entrapment level of 85.24% along with a drug release of 92.12%. Carbopol 940, 1.5% was used to make the topical gel. The results of biochemical studies reflected that griseofulvin-loaded-nanogel produced a more significant decrease in lipid peroxidation as compared to the standard drug. The in-vitro cytotoxicity studies showed better safety of nanogel in human keratinocyte cells (HaCaT). The results of antifungal activity showed complete clinical and mycological cure in a duration of 21 days against superficial infections like Tenia pedis and also ringworm in Wistar rats while using T.rubrum and M.canis fungal strains. These preclinical investigations have proved that the nanogels have a better potential in treating the aforementioned superficial infections providing an effective alternative for currently existing products.

Design and optimization of lomefloxacin loaded NLC gel for ophthalmic drug delivery

Lomefloxacin is a fluoroquinolone drug that has broad-spectrum action against Gram-negative as well as Gram Positive pathogens. The drug retention issues of ophthalmic drug delivery are a key parameter to select NLC gel as a deliver system. The purpose of the present investigation was to design, optimize and evaluate Lomefloxacin loaded nano structured lipid gel for Ophthalmic Drug Delivery. Lomefloxacin loaded NLCs were prepared by high-pressure homogenization approach (hot), using Olive oil as liquid lipid, Stearic acid as solid lipid and tween 80 as surfactant. Box-Behnken design was used to optimize Lomefloxacin loaded NLCs using Design-Expert 12 programme. Lipid ratio X1, surfactant concentrationX2, and homogenization cycle X3 are kept as three independent variables particle size (Y1 nm), entrapment efficiency (Y2 percent), and drug release percentage (Y3 percent) as dependent variables. NLCs were characterized for particle size, zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated.

The Nanostructured lipid carrier gel of Oroxylin A reduced UV-induced skin oxidative stress damage

Oxidative stress damage caused by sun exposure damages the appearance and function of the skin, which is one of the essential inducements of skin aging and even leads to skin cancer. Oroxylin A (OA) is a flavonoid with excellent antioxidant activity and has protective effects against photoaging induced by UV irradiation. However, the strong barrier function of the skin stratum corneum prevents transdermal absorption of the drug, which limits the application of OA in dermal drug delivery. Studies have shown that nanostructured lipid carriers (NLC) can promote not only transdermal absorption of drugs but also increase drug stability and control drug release efficiency, which has broad prospects for clinical applications. In this paper, NLC loaded with OA (OA-NLC) was prepared in order to improve the skin permeability and stability of OA. In vitro studies revealed that OA-NLC had better therapeutic effects than OA solution (OA-Sol) in the cellular model of UVB radiation. OA-Sol and OA-NLC were immobilized in a hydrogel matrix to facilitate application to the dorsal skin of mice. It was found that OA-NLC-gel showed significant antioxidant and anti-apoptotic activity compared to OA-Sol-gel, which was able to protect against skin damage in mice after UV radiation. These results suggest that OA-NLC can improve the deficiencies of OA in skin delivery and show better resistance to UV-induced oxidative damage. The application of OA-NLC to skin delivery systems has good prospects and deserves further development and investigation.

Nanostructured lipid carrier based dermal gel of cyclosporine for atopic dermatitis-in vitro and in vivo evaluation

Cyclosporine is a gold standard for the treatment of atopic dermatitis. Patients demand extended therapy without adverse effects as atopic dermatitis is a chronic condition. The objective of the study was to formulate and evaluate nanostructured lipid carriers (NLC) based dermal gel of cyclosporine to improve transdermal permeation and achieve targeted delivery. Based on drug solubility, excipients were selected for NLCs, namely; Compritol ATO 888®, Gelucire 44/14® as solid lipids, Miglyol 812 N® as liquid lipid and Solutol HS 15® as surfactant. 22 full-factorial design was used for statistical optimization and optimized batch (NLC-01) with particle size 265.6 nm and zeta potential −29.9 mV incorporated into Carbopol-934 gel to prepare cyclosporine NLC based gel. The pH of the gel was found in the range of 5.2–5.5 which was suitable for skin application and in vitro diffusion study showed complete drug release at the end of 6 h. In skin irritation studies, NLC gel and placebo gel did not cause any redness or irritation to the rat skin. Further, NLC based gel was applied for one week on dermatitis-induced rat skin. Post-NLC based gel treatment, the disappearance of erythema and approximately two-fold reduction in ear flap thickness was observed compared to the disease control group. Therefore, NLC based cyclosporine gel can be explored as an alternative dermal treatment of atopic dermatitis.

Nanostructured lipid carrier for transdermal gliclazide delivery: development and optimization by Box-Behnken design

The aim of current study was to prepare and optimize the nanostructured lipid carrier (NLC) for transdermal gliclazide (GCZ) delivery. The melt emulsification followed by ultrasonication technique was utilized to prepare GCZ–loaded-NLC. The optimization of NLC was achieved by Box-Behnken design. The surfactant (Tween 20) % (X1), total lipid (glyceryl monostearate + Lauroglycol™ 90) % (X2), and sonication time (min) (X3) were chosen as independent variables, while particles size (Y1), polydispersity index (Y2), and entrapment efficiency (Y3) were selected as response. Further, the prepared NLC was estimated for in vitro drug release study, ex vivo skin permeation and confocal laser scanning microscopy (CLSM) studies. Results of present study demonstrated that the optimized GCZ loaded NLC formulation presented the particles size, polydispersity index, zeta potential, and entrapment efficiency of 120.4 nm, 0.316, −5.58 mV, and 87.32% respectively. The in vitro drug release study indicated drug release of 68.27 ± 2.98% and 45.87 ± 2.85% for GCZ-NLC and conventional GCZ dispersion respectively. The GCZ-NLC-Gel formulation exhibited transdermal drug permeation of 76.89 ± 2.52% as compared to conventional gel (45.65 ± 2.79%). The CLSM of rat skin treated with NLC gel exhibited a deeper permeation (35 μm) in comparison to the conventional gel (15 μm). In conclusion, GCZ loaded NLC was successfully optimized using Box-Behnken design that contributed many advantages over conventional formulation and thus demonstrating NLC as propitious carriers for the transdermal GCZ delivery.

Development and evaluation studies of Corylin loaded nanostructured lipid carriers gel for topical treatment of UV-induced skin aging

We prepared nanostructured lipid carriers (NLC) to promote skin permeation of Corylin so that it can increase its effect on photoaging. Corylin-NLCs were prepared and characterized based on morphology, particle size, zeta potentials, FTIR and DSC. In vitro, we assess the cytotoxicity and lactate dehydrogenase (LDH) of HaCaT cells irradiated by UVB. Expression of antioxidant enzymes was evaluated by commercial kits. The effects of Corylin-NLC on apoptosis were confirmed by flow cytometry and western blotting. In vivo, we use UV irradiated mouse as the oxidative stress model to assess the therapeutic effect of Corylin loaded NLC gel. We identified the Corylin-NLCs can significantly suppress the LDH release, decrease MDA content, increase in CAT, SOD, GSH-Px activity, increase the expression of Bcl-2/Bax protein and reduce the expression of cleaved caspase-3/caspase-3 protein on UVB induced HaCaT cells. The histopathological lesions were significantly improved and observably decreased MDA level, increase in antioxidant enzymes activity in serum of mice by pretreatment of Corylin-NLCs gel. Overall, this study proposes a promising strategy for improving the therapeutic efficacy of photoaging.

Berberine loaded dermal quality by design adapted chemically engineered lipid nano-constructs-gel formulation for the treatment of skin acne

The study's purpose intended to develop and optimize an NLC formulation for topical berberine administration with increased skin acne efficacy. The “three-parameters, three-level Box-Behnken design” was employed to improve the formulation based on vesicle size, PDI, and encapsulation efficiency. In-vitro profile for drug release, skin penetration investigation using confocal microscopy, skin irritation, anti-inflammatory, and anti-acne studies were performed on the optimized formulation. The vesicles with a size of 132.5 ± 10.34 nm, PDI of 0.224 ± 5.12, and entrapment efficiency of 85.956 ± 5.78% were found in the optimized formulation. The optimized formulation had spherical vesicles, according to TEM imaging. In vitro release studies showed that final optimized NLC formulation has cumulative release of drug (72.675 ± 3.686%), which was significantly greater as compared to NLC gel formulation (48.354 ± 4.893%). Thermo-analytical studies of NLCs formulation determined smooth drug interaction via rat skin membrane. Confocal microscopy revealed that, rhodamine-NLC formulation was traceable up to 54.9 μm across skin of rats, while solution of rhodamine penetrated only up to 20.4 μm of rat skin. Skin irritation study further showed significantly lower irritation level of skin (erythema: 0.50.231 and edema: 0.50.320) by applying optimized NLC-gel formulation compared to the control irritant. Furthermore, in comparison to the positive control, the anti-acne study demonstrated a decrease in all acne parameters, in addition to higher effectiveness over the commercially available formulation. These findings suggest that developed berberine loaded NLC gel could be a promising vehicle for the safe and effective topical administration of drugs to treat acne vulgaris.

Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration.

Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients.

Formulation and Evaluation of Clarithromycin Loaded Nanostructured Lipid Carriers for the Treatment of Acne

Background: Clarithromycin is a macrolide antibiotic used in acne treatment, but it has poor solubility, which decreases its permeability through lipid barriers such as skin. Nanostructured lipid carriers can enhance the permeability of clarithromycin through the skin, thus improving its potential for controlling acne.
 Aim: To formulate and evaluate Nanostructured lipid carriers of clarithromycin for topical delivery in acne treatment
 Methods: Nanostructured lipid carriers were prepared by emulsification and ultrasonication methods using lipids such as glycerol monostearate and oleic with poloxamer 188 as stabilizer. These nano-carriers were optimized with the help of the Quality by Design (QbD) approach employing Design-Expert® software. The nanoparticles were characterized for particle size analysis, zeta potential, drug-excipient compatibility, entrapment efficiency, and surface morphology by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The nano-carriers were also investigated for in vitro drug release and ex vivo permeation through excised goat skin. The optimized formulation was incorporated into topical carbopol gel base, formulated and examined for pH, viscosity, spreadability, in vitro drug release, ex vivo permeation, and stability under accelerated conditions.
 Results: The average particle size of the optimized nanoparticles was 164.8 nm, and zeta potential was -39.2 mV. FTIR studies showed that drug and lipids are compatible with each other. The morphology study by SEM and TEM showed spherical shaped particles. The entrapment efficiency of the optimized formulation was found to be 88.16%. In vitro drug release studies indicated sustained release from the formulation due to diffusion through the lipid matrix of the particles. The ex vivo permeation study using goat skin produced greater permeation from the NLC gel (89.5%) than marketed gel (65%) due to the lipid solubility of the nanoparticles in the skin. The formulation was stable under accelerated conditions.
 Conclusion: The optimized formulation can be considered as promising nano-carriers suitable for the sustained release of clarithromycin into the skin for effective control of acne.

A NOVEL NANOGEL FORMULATION OF FINASTERIDE FOR TOPICAL TREATMENT OF ANDROGENETIC ALOPECIA: DESIGN, CHARACTERIZATION AND IN VITRO EVALUATION

Objective: The present paper describes the development and evaluation of a Novel Finasteride (FSD) nanogel topical delivery for the treatment of Androgenetic Alopecia. Nano-based topical formulation was chosen to enhance the solubility, permeability, biocompatibility of drug and to overcome the problems associated with the oral delivery of finasteride.
 Methods: Various trails batches were prepared by using probe sonication method. Based on stability studies and particle size, NP4 trail was optimized which exhibited a spherical shape with a mean diameter of 113.80±0.72, the polydispersity of 0.28±0.01, zeta potential of-25.2 mV, drug entrapment efficiency of 92.67±0.47 %, and drug loading of 6.15±0.02 %. Storage stability studies demonstrated that the particle size and entrapment efficiency were not changed during 3 mo both at 4 °C and room temperature. Finasteride (FSD) NLCs were characterized for particle size by scanning electron microscope (SEM), chemical state by X-Ray diffraction (XRD), physical stability by centrifugation and thermodynamic stability by Freeze-thaw method. These prepared nanoparticles were transformed into topical nanogel and further evaluated.
 Results: Among the different trails, C2 trail of NLC gel has shown excellent gelling capacity, clear appearance, good viscosity characteristics and was selected for further evaluation studies. Batches of topical nanogel were characterized through pH, homogeneity, spreadability, viscosity, drug content and in vitro drug release study. Based on pH (6.5-6.8), drug content (91.25±0.9%), spreadability (6.7 cm/sec), C2 batch was subjected to In vitro skin occlusivity study, in-vitro release study and In vitro heamolysis study.
 Conclusion: The percent cumulative drug release for Finasteride (FSD) gel was found to be 758.52±1.49 µg at 24 h which is quite higher than plain gel and Finasteride (FSD) gel showed maximum occlusiveness and excellent spreadability and found to be stable. In conclusion, prepared Finasteride (FSD) Nanogel could be used with promising potential for the treatment of Androgenetic Alopecia.

Topical Delivery of Apremilast Loaded Nanostructured Lipid Carrier Based Hydrogel for Psoriasis Therapy

Background: Apremilast (APR) is an orally administered selective phosphodiesterase 4 inhibitor approved to treat plaque psoriasis and psoriatic arthritis and is available as an oral tablet formulation. However, its systemic side effects limit its application. The low solubility and permeability of apremilast make it difficult to administer it through the skin. Hence an attempt is made to incorporate apremilast into a suitable nanocarrier to facilitate its topical delivery.
 Aims: To formulate and characterize Apremilast loaded nanostructured lipid carriers for the management of psoriasis to reduce the systemic side effects.
 Methodology: Apremilast loaded Nanostructured Lipid carriers (NLC) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Sefsol 218, Tween 80 and Transcutol P as Solid Lipid, Liquid lipid, Surfactant and Penetration Enhancer. The NLC was incorporated into carbapol 934 dispersion to convert it into a gel. The NLC formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the NLC gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, Skin deposition and In vivo studies.
 Results: The formulated Apremilast loaded showed particle size of less than 200 nm (i.e.170.32nm) with a narrow PDI of 0.267. Entrapment efficiency revealed that 89.26±01.22% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the nanocarrier. The extended-release pattern of the formulated NLC for 24h was observed in the in vitro release studies and followed the Higuchi model(R2=0.9966). Ex vivo permeability showed a 6.14 fold increase in permeability and 74.05±0.25% deposition of apremilast loaded NLC gel compared to apremilast gel. The formulation was stable for three months without significant changes. In vivo skin studies showed that the prepared NLC did not have any skin irritation potential. The antipsoriatic activity demonstrated by the Apremilast loaded NLC gel in the imiquimod induced psoriasis model in mice was comparable to the standard treatment.
 Conclusion: Apremilast loaded NLC demonstrated enhanced permeation, improved skin retention and extended-release compared to conventional gel. The developed formulation can be an alternative for psoriasis therapy after clinical trials in the future.

A resveratrol-loaded nanostructured lipid carrier hydrogel to enhance the anti-UV irradiation and anti-oxidant efficacy

Exposure to ultraviolet (UV) irradiation leads to the generation of reactive oxygen species (ROS) and DNA damage in skin tissue, which can further result in skin cancers. Using sunscreens is one of the most popular and the most effective method to resist UV irradiation. Resveratrol (RES) shows high absorbance in UV region and significant anti-oxidant effects. However, RES is easily degraded by UV irradiation, resulting in the decrease of bioactivity and the limitation of its application in the pharmaceutical preparations of skin. In this paper, a nanostructured lipid carrier gel loaded with RES (RES-NLC-gel) was prepared to improve the stability of RES and the accumulation of RES in the epidermis. Moreover, RES-NLC-gel could scavenge free radical effectively and protect human keratinocyte from UV irradiation by inhibiting the generation of ROS, decreasing the protein expression of cleaved caspase-3 and Bax and increasing the protein expression of Bcl-2. When mice skin was pretreated with RES-NLC-gel, there were less erythema, wrinkles and scabs on mice skin. The epidermal thickness of mice skins obviously reduced in dose-dependent manner. The activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in mice skin tissue significantly increased. Thus, RES-NLC-gel exhibited an obvious anti-UV irradiation and anti-oxidant activity in vivo. RES-NLC-gel displayed great application potential in protecting skin from UV irradiation.

Combinatorial lipid-nanosystem for dermal delivery of 5-fluorouracil and resveratrol against skin cancer: Delineation of improved dermatokinetics and epidermal drug deposition enhancement analysis

In the present study, combinatorial nanostructured lipid carrier gel of 5-fluorouracil and resveratrol was formulated, optimized and characterized to enhance permeation in between epidermis and dermis layers of the skin to obtain a synergistic effect against skin cancer. After extensive trials, a newly modified emulsiosonication method was developed and additionally, for the first time, stability studies were done in the beginning to optimize formulation technique, which exhibited two major benefits simultaneously; first, it provided best-optimized technique for preparation of combinatorial lipid-nanosystem, and secondly, it also demonstrated a detailed report card of durability of formulations. In vitro release study showed a significantly improved, slow and prolonged release of drugs from the optimized lipid-nanosystem (***p < 0.05), which followed non-Fickian Higuchi kinetics. Besides, mechanism of skin permeation enhancement study, dermatokinetic assessment, and depth analysis of optimized formulation on skin exhibited improved permeation and well distribution of drugs up to the dermis layer of skin. Moreover, combinatorial linogel possessed significantly greater efficacy (**p < 0.01) on the A431 cell line, as compared to the conventional formulation. Thus, findings revealed that modified method of preparation for dual drug-loaded lipid-nanosystem lead to the production of a stable formulation that also improved the retention of both 5-fluorouracil and resveratrol in between the epidermis and dermis region of skin thereby helping in the management and treatment of skin cancer.

Development of Sertaconazole Nitrate Loaded Nanostructured Lipid Carriers Gel Using Central Composite Design: In vitro and Ex vivo Evaluation

Aim: The aim of this study was to develop effective topical antifungal formulation containing sertaconazole nitrate. Background: Sertaconazole nitrate, a topical antifungal, was incorporated in solid-liquid lipid nanostructures and gelled further for topical application. Objective: The objective of this investigation was to develop a topical formulation containing sertaconazole nitrate which was incorporated in the solid-state of the matrix to prolong the release in deep skin infection and hence reduce the application frequency. Methods: The nanostructured lipid carriers of sertaconazole nitrate were developed by high-speed homogenization followed by ultrasonication using Estosoft-GTS® (glyceryl tristearate) as a solid lipid, oleic acid as liquid lipid and Tween 80 as an emulsifier. The central composite design was used to optimize total lipid concentration and fraction of liquid lipid in the total lipid and its effect on entrapment efficiency and drug release was determined. Results: The carrier particles had an average size of 366.3 nm; entrapment efficiency in between 50.66% to 87.36%; cumulative drug release up to 92.90% and zeta potential of 7.43 mV. Characterization by FTIR indicated no negative interaction between drug and excipients, XRD showed the disappearance of crystalline peaks of the encapsulated drug while DSC revealed complete solubilization of the drug. About 99.6% of the drug was estimated by HPLC method. The drug release from gel and cream was 25.04% and 72.97% respectively. The lipid and gel excipients did not interfere with the antifungal activity of the drug. Conclusion: The developed nanocarriers loaded gel was stable. It prolonged the drug release (for 24 h) than marketed cream. It could be a promising concept for the topical delivery of antifungal and anti-inflammatory materials.

Nanophyto-gel against multi-drug resistant Pseudomonas aeruginosa burn wound infection

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

Development and Optimization of Luliconazole Nanostructured Lipid Carriers Based Gel by Quality by Design its Skin Distribution Studies, Dermatokinetic Modeling & In-Vitro and Ex-Vivo Correlation.

The present study was aimed to improve the permeability of Luliconazole (LZ) and to localize high drug concentrations at skin layers by Quality by Design (QbD) based Nanostructured lipid carriers (NC) based gel. Quality Target Product Profile was set, and Critical Quality attributes were identified. FT-IR and DSC studies confirmed compatibility. Risk assessment was carried out by screening the factors using 2IV7-2 fractional factorial design and optimization by Box Behnken design. Cholesterol: Cetyl Palmitate, PEG 200 and probe sonication time were identified as factors, Particle size (<200 nm), PDI (0.4), % Entrapment efficiency (% EE, >80%) and % Cumulative Drug release (% CDR, >95%) as responses. Contour plots, overlay plots and desirability, were utilized to create design space. The quadratic polynomial equations showed increased lipid content, PEG 200 and optimum sonication time reduced particle size, PDI, improved % EE and % CDR. The optimized formula was formulated into a gel. Ex-vivo permeation studies performed using pig ear pinna skin revealed that developed LZ NC gel exhibited greater permeation 272.98±8.57 (μg/cm2) and 32.11 ±4.7 (μg/cm2/h) flux than plain drug dispersed gel. Dermatokinetic parameters of LZ NC gel revealed that a highly significant amount of LZ was permeated, distributed and transported through the skin layers. The better linear correlations were obtained by LZ permeation through a synthetic membrane (in-vitro) and pig ear pinna skin (ex-vivo). The above findings revealed that developed LZ NC gel exhibited better permeation and localization at skin layers in treating fungal infections.