Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-Like Skin Inflammation in an Animal Model

Psoriasis, a chronic inflammatory illness, is on the rise and is linked to several other life-threatening diseases. The primary goal of this study was to create a nanoemulsion gel loaded with methotrexate and olive oil (MTX NEG). The formulation was evaluated for physicochemical characterization, entrapment efficiency, drug release kinetics, skin permeation studies and stability tests. In addition, the efficacy of MTX NEG against psoriasis was tested using imiquimod-induced psoriasis in a rat model. The final optimized MTX NEG was developed with a particle size of 202.6 ± 11.59 nm and a PDI of 0.233 ± 0.01, with a 76.57% ± 2.48% average entrapment efficiency. After 20 h, the release kinetics predicted a 72.47% drug release at pH 5.5. FTIR findings demonstrated that the optimized MTX NEG formulation effectively fluidized both the epidermis and dermis of the skin, potentially increasing drug permeability and retention. The application of Tween 80 and PEG 400, on the other hand, significantly enhanced these effects, as these are well known penetration enhancers. After 24 h, an average of 70.78 ± 5.8 μg/cm2 of methotrexate was permeated from the nanoemulsion gel with a flux value of 2.078 ± 0.42 μg/cm2/h, according to permeation measurements. Finally, in vivo experiments on rabbit skin revealed that the increased skin penetration of methotrexate-loaded nanoemulsion gel was not due to structural alterations in intercellular lipid layers in the stratum corneum. In vivo antipsoriatic studies on rats revealed that MTX NEG produced a PASI decrease that was extremely similar and even better than the 91% reduction seen in the MTX tablet group. According to the pharmacokinetic profile, Cmax was 8.5 μg/mL, Tmax was 12 h, and t1/2 was 15.5 ± 2.37 h. These findings reinforce that MTX-NEG based on olive oil could be a possible treatment for psoriasis and could decrease the remission of psoriasis-like symptoms.

DEVELOPMENT AND IN VITRO ASSESSMENT OF BUSPIRONE LOADED IN SITU NANOEMULSION GEL

Objective: Buspirone, is a medication primarily used for generalized anxiety disorder (GAD), relieve symptoms of anxiety and unipolar depression. This drug exhibit low bioavailability (approximately 5%) due to extensive first-pass metabolism and non-targeted delivery results in numerous side effects. It is taken by mouth, and it may take up to four weeks to have an effect. The present investigation aimed at the development of buspirone in situ nanoemulsion gel to evaluate its potential for efficacious nose to brain drug delivery. Methods: Buspirone-loaded nanoemulsions (BNEs) were prepared by aqueous titration (Spontaneous emulsification) method using Oleic acid, Tween 80, and PEG 400 as oil, surfactant and cosurfactant respectively. The NEs (FC1-FC8) were characterized for pharmaceutical characteristics (Appearance, thermodynamic stability, polydispersity index (PDI) value, globule size, pH, Viscosity, Conductivity and Refractive index). In vitro drug release study from nanoemulsions (NEs) was carried out using Keshary–Chien cell (KC cell, 25 ml) in phosphate buffer pH 5.5. Results: Formulation FC5 with mean globule size of 105.4±1.10 nm, PDI value 0.230±0.01 and drug release 90±0.39% in 6 h (h) was developed as mucoadhesive nanoemulsion gel formulation with 17.5 % W/W of Pluronic F127. The nanoemulsion gel was homogenous, transparent, and possessed a bioadhesive strength of 1605 Dyne/cm2. In vitro cumulative drug release was found to be 90.00±0.39 % at the end of 6 h. Conclusion: The gel had no effect on the structural integrity of nasal mucosa. Hence, the study postulates that In situ nanoemulsion gel of buspirone could be used as an intranasal formulation for targeted brain delivery via nasal route.

Ligusticum sinense Nanoemulsion Gel as Potential Repellent against Aedes aegypti, Anopheles minimus, and Culex quinquefasciatus (Diptera: Culicidae)

Ligusticum sinense Oliv. cv. is a species of Umbelliferae (Apiaceae), a large plant family in the order Apiales. In this study, L. sinense hexane extract nanoemulsion gel (LHE-NEG) was investigated for mosquito repellency and compared to the standard chemical, N,N-diethyl-3-methylbenzamide (DEET), with the goal of developing a natural alternative to synthetic repellents in protecting against mosquito vectors. The results demonstrated that LHE-NEG afforded remarkable repellency against Aedes aegypti, Anopheles minimus, and Culex quinquefasciatus, with median protection times (MPTs) of 5.5 (4.5–6.0), 11.5 (8.5–12.5), and 11.25 (8.5–12.5) h, respectively, which was comparable to those of DEET-nanoemulsion gel (DEET-NEG: 8.5 (7.0–9.0), 12.0 (10.0–12.5), and 12.5 (10.0–13.5) h, respectively). Evaluation of skin irritation in 30 human volunteers revealed no potential irritant from LHE-NEG. The physical and biological stability of LHE-NEG were determined after being kept under heating/cooling cycle conditions. The stored samples of LHE-NEG exhibited some changes in appearance and differing degrees of repellency between those kept for 3 and 6 heating/cooling cycles, thus providing slightly shorter MPTs of 4.25 (4.0–4.5) and 3.25 (2.5–3.5) h, respectively, when compared to those of 5.0 (4.5–6.0) h in fresh preparation. These findings encourage commercially developed LHE-based products as an alternative to conventional synthetic repellents in preventing mosquito bites and helping to interrupt mosquito-borne disease transmission.

Formulation and Evaluation of DHA Oil based Nicotinamide Nanoemulsion Gel for Treating Atopic Dermatitis

Background: Atopic dermatitis (or eczema) can be defined as a chronic inflammatory condition accompanied by severe pruritus. Objective: The prepared gel was evaluated for in vitro drug release, in vitro occlusion studies, transepidermal water loss studies, skin permeation studies, in vitro skin irritation studies and antiinflammatory cell line studies. Methods: In vitro drug release studies were performed using Franz diffusion cells. The in vitro occlusion studies were carried out by the procedure reported by Wissing et al. TEWL determination was done by the method proposed by Reiger. The skin permeation studies were carried out using porcine skin using Franz diffusion cells. In vitro skin irritation study was carried out using HETCAM (Hen’s Egg Test on the Chorioallantoic Membrane) method. Anti-inflammatory cell line studies were carried out using RAW 264.7 cell lines. Results: In vitro drug release studies,drug release of nicotinamide from nanoemulsion gel was found to be more than marketed gel. Kinetic modelling showed a higuchi model with non-fickian diffusion. In vitro occlusion study showed the percentage of evaporated water from prepared nanoemulsion formulation after 72 h is very less compared with the other formulations. The TEWL measurement shows the reduction in TEWL has more in prepared nanoemulsion gel than other formulations. Anti-inflammatory cell line studies proved that the nanoemulsion gel has inhibition capacity on COX activity, LOX activity, Inducibe nitric oxide synthase and cellular nitrate levels. Conclusion: DHA oil based nicotinamidenanoemulsion gel were prepared successfully and the evaluation of prepared gel showed better drug release and skin permeation with better antiinflammatory activity.

Nanoemulsion Gel Formulation Optimization for Burn Wounds: Analysis of Rheological and Sensory Properties

Background: Despite the variety of treatment methods for wounds and scars after burns, there are still few effective preparations that can be used in a non-invasive therapy. Recent years have seen significant development of nanomedicine and nanotechnology in the treatment of infection in burn wounds. Proposal: The aim of this work was to develop a formula of a nanoemulsion gel for skin regeneration after burns, and to compare its rheological and sensory properties, as well as the effectiveness of post-burn skin regeneration with preparations available on the market. Methods: At the first stage of studies the composition and parameters of the preparation of sea buckthorn oil-based O/W (oil-in-water) nanoemulsion containing hyaluronic acid and aloe vera gel, as the active ingredients were optimized. Then, the nanoemulsion was added to the gel matrix composed of carbomer (1%) and water which resulted in receiving nanoemulgel. The physicochemical parameters of the obtained samples were characterized by means of dynamic light scattering method and scanning electron microscope. Rheological, sensory and influence on skin condition analysis was conducted for selected market products and developed nanoemulgel. Results: Nanoemulsion gel (d = 211 ± 1.4 nm, polydispersity index (PDI) = 0.205 ± 0.01) was characterized by semi-solid, non-sticky consistency, porous structure, law viscosity, good “primary” and “secondary” skin feelings and pleasant sensorical properties. It improves the condition of burned skin by creating a protective layer on the skin and increasing the hydration level. Conclusion: Due to the fact that the obtained nanoemulsion gel combines the advantages of an emulsion and a gel formulation, it can be a promising alternative to medical cosmetics available on the market, as a form of formulation used in skin care after burns.

Dual Asymmetric Centrifugation Efficiently Produces a Poloxamer-Based Nanoemulsion Gel for Topical Delivery of Pirfenidone

This study used dual asymmetric centrifugation (DAC) to produce a topical vehicle for Pirfenidone (Pf; 5-methyl-1-phenyl-2[1H]-pyridone)—a Food and Drug Administration-approved antifibrotic drug indicated for idiopathic fibrosis treatment. Pf was loaded (8 wt%) in a poloxamer nanoemulsion gel (PNG) formulation consisting of water (47.8 wt%), triacetin (27.6 wt%), poloxamer 407 (P407, 13.8 wt%), polysorbate 80 (1.8 wt%), and benzyl alcohol (0.9 wt%). To our knowledge, poloxamer gels are typically processed with either high-shear methods or temperature regulation and have not been emulsified using DAC. Using a single-step emulsification process, 2 min mixed at 2500 RPM resulted in the lowest Pf loading variability with a relative standard deviation (RSD) of 0.96% for a 1.5 g batch size. Batch sizes of 15 g and 100 g yield higher RSD of 4.18% and 3.05%, respectively, but still in compliance with USP guidelines. Ex vivo permeation in full thickness porcine skin after 24 h showed total Pf permeation of 404.90 ± 67.07 μg/cm2. Tested in vitro on human dermal fibroblasts stimulated with transforming growth factor-beta 1 (TGF-β1), Pf-PNG resulted in a > 2 fold decrease in α-SMA expression over vehicle control demonstrating that formulated Pf retained its biological activity. One-month stability testing at 25°C/60% relative humidity (RH) and 40°C/75% RH showed that % drug content, release kinetics, and biological activity were largely unchanged for both conditions; however, pH decreased from 6.7 to 5.5 (25°C/60% RH) and 4.5 (40°C/75% RH) after 1 month. Overall, these data demonstrate the utility of DAC to rapidly and reproducibly prepare lab-scale batches of emulsified gels for pharmaceutical formulation development.