Plain Gel Research Articles

Comparative Study on Enhanced Skin Permeation Efficiency of Phenylephrine via Novel Lipid Vesicles: A Promising Approach in Preventing Chemotherapy-Induced Alopecia Management.

Chemotherapy-induced alopecia (CIA) significantly impacts patients' emotional and psychological well-being and treatment regimen. Phenylephrine, a topical vasoconstrictor, can potentially reduce hair loss by limiting chemotherapy drug delivery to hair follicles. However, effective delivery of Phenylephrine through the skin remains challenging. This study investigates lipid vesicles as delivery vehicles to enhance Phenylephrine's skin permeation and sustained release due to their biocompatibility and encapsulation capabilities. This study aimed to formulate and compare different lipid vesicles of Phenylephrine HCl for enhanced permeation through the skin for deep dermal delivery with sustained release of the drug so as to achieve local vasoconstriction. Phenylephrine-loaded ethosomes, invasomes, and transfersomes were prepared and characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE %). These lipid vesicles were incorporated into hydrogels to facilitate sustained drug release to deep dermal layers where they could target local vasculature and cause vasoconstriction. The prepared vesicular gels were evaluated for various permeation parameters. The entrapment efficiencies of the developed vesicles ranged from 49.51 ± 3.25% to 69.09 ± 2.32%, with vesicle sizes ranging from 162.5 ± 5.21 nm to 321.32 ± 3.75 nm. Statistical analysis revealed significantly higher flux values (Jss, μg/cm2 h) of 0.6251, 0.6314, and 0.4075 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, compared to plain gel (0.1254) (p < 0.005). The enhancement factors were 4.9848, 5.0350, and 3.2496 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, indicating superior permeation abilities of ethosomal and invasomal formulations. The results demonstrate that ethosomal and invasomal formulations were efficient in delivering the drug to deep dermal layers of skin in a sustained manner. These findings suggest that these Lipidic vesicles would be able to target the local vasoconstrictor to vasculature, causing reduced hair loss by limiting chemotherapy drug delivery to hair follicles and managing chemotherapy-induced alopecia.

Green formulation of Menadione-loaded niosome as a skin-lightening preparation: In vitro/In vivo safety evaluation on Wistar rat

Purpose: In the present research, a green technique (an ultrasonic method) was used to synthesize menadione sodium bisulfite (MSB) niosome (Menasome) which is used to improve dermal delivery and increase anti-melanogenesis activities. Methods: Various cholesterol: surfactant (Chol: Sur) ratios were investigated to optimize the Menasomes. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of MSB in nanoparticle form. Additionally, the optimized formulation was used to investigate ex-vivo skin absorption, in vivo skin irritation, in vitro cell survival, and anti-melanogenesis activity. Results: The results exhibited that increasing cholesterol (Chol) declined the average size of the Menasomes from 653.766±25.171 nm to 298.133±8.823 nm and increased entrapment efficiency 30.237±3.4204% to 83.616±2.550 %. The rat skin permeation study indicated that Menasome gel administered more MSB in dermal layers (439.000±36.190μg/cm2 or 23.827±1.964%) than MSB plain gel (286.200± 22.6μg/cm2 or 15.53±1.227%). In both the in vivo skin irritation test and the in vitro cytotoxicity experiment, the extended-release behavior of the enhanced Menasome demonstrated a minimal side effect profile. Furthermore, optimum Menasome inhibited melanin formation (37.426± 1.644% at 15μM) greater than free MSB (57.383±1.654%) considerably (p &lt;0.05). Furthermore, Menasome 7 prevented L-dopa auto-oxidation in higher levels (95.140±2.439%) than pure MSB solution (83.953±1.629%). Conclusion: According to the study's findings, the prepared Menasome could be employed as a viable nanovehicle for MSB dermal delivery, a promising solution for the management of human hyperpigmentation disorders.

Development and evaluation of nanoemulsion gel loaded with bioactive extract of Cucumis melo var. agrestis: A novel approach for enhanced skin permeability and antifungal activity

The utilization of phytoconstituents in skin care products has emerged as a notable trend due to their recognized safety and therapeutic efficacy. However, the challenge lies in improving the effective delivery of phytoconstituents to specific tissues, primarily attributed to their poor solubility and low permeability. This study endeavors to address this challenge by developing, optimizing and characterizing Cucumis melo var. agrestis (CME) extract loaded nanoemulsion gel (CME-NEG), aiming to enhance the skin permeability and antifungal activity. Herein, nanoemulsions encapsulating the plant extract were prepared using ultrasonication technique and were characterized for droplet size, zeta potential, polydispersity index (PDI) and entrapment efficiency. Further, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis were conducted to characterize the optimized CME extract loaded nanoemulsion (CME-NE 3) formulation. The optimized formulation was blended with Carbopol 940 gel to develop CME-NEG, which was evaluated for release kinetics, in vitro permeation and in vitro antifungal activity. High performance liquid chromatography (HPLC) analysis confirmed the presence of gallic acid, chlorogenic acid, 4-Hydroxy benzoic acid (HB acid), kaempferol, caffeic acid and quercetin. Findings of 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that the ethanolic extract had highest antioxidant activity (88.88 %). The optimized formulation displayed smooth spherical nanodroplets with size of 175.5 ± 1.56 nm, zeta potential of −21.5 ± 0.12 mV, PDI of 0.192 ± 0.06, and highest entrapment efficiency (EE) of 91.35 ± 1.65 %. The release profile of CME-NE exhibited a controlled release characteristic and the release kinetic mechanism was best described by the Korsmeyer-Peppas (Kp) model. In a 24 h permeation study, it was observed that the in vitro permeation of CME-NEG was 58.63 %, significantly higher than that of CME extract loaded plain gel (CME-PG) with an enhancement ratio of 2.12. The prepared CME-NEG formulation also presented enhanced antifungal activity as compared to pure CME extract. In conclusion, the designed CME-NEG offers a promising topical drug delivery system with enhanced skin permeability and antifungal activity.

PH-Sensitive In Situ Gel of Mirtazapine Invasomes for Rectal Drug Delivery: Protruded Bioavailability and Anti-Depressant Efficacy.

The present research emphasizes fabrication alongside the assessment of an innovative nano-vesicular membranous system known as invasomes (NVMs) laden with Mirtazapine for rectal administration. This system could circumvent the confines of orally administered counterparts regarding dose schedules and bioavailability. Mirtazapine invasomes were tailored by amalgamating phospholipid, cineole, and ethanol through a thin-film hydration approach rooted in the Box-Behnken layout. Optimization of composition parameters used to fabricate desired NVMs' physicochemical attributes was undertaken using the Design-Expert® program. The optimal MRZ-NVMs were subsequently transformed to a pH-triggered in situ rectal gel followed by animal pharmacodynamic and pharmacokinetic investigations relative to rectal plain gel and oral suspension. The optimized NVMs revealed a diameter size of 201.3 nm, a z potential of -28.8 mV, an entrapment efficiency of 81.45%, a cumulative release within 12 h of 67.29%, and a cumulative daily permeated quantity of 468.68 µg/cm2. Compared to the oral suspension, pharmacokinetic studies revealed a 2.85- and 4.45-fold increase in calculated rectal bioavailability in circulation and brain, respectively. Pharmacodynamic and immunohistopathology evaluations exposed superior MRZ-NVMs attributed to the orally administered drug. Consequently, rectal MRZ-NVMs can potentially be regarded as a prospective nanoplatform with valuable pharmacokinetics and tolerability assets.

Preparation of arbutin hydrogel formulation as green skin lightener formulation: in vitro and in vivo evaluation

A hydrogel formulation containing arbutin was developed for use as a topical cosmetic product aimed at enhancing the anti-melanogenesis effect and skin delivery. To develop Arbutin-hydrogel, 1% arbutin was incorporated into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the arbutin-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, toxicity study and, skin absorption test were employed to assess the arbutin-hydrogel. The swelling percentages of arbutin-hydrogel increased significantly after 4 h. In vitro, cytotoxic activity revealed that arbutin-hydrogel has no toxicity. Also, the cutaneous penetration investigation revealed that arbutin-hydrogel had a superior cutaneous accumulation (42.25 ± 0.30%) compared to plain gel (16.80 ± 0.33%). Also, physico-chemical specifications assay and solid state assessment were employed to assess of optimum formulation. Arbutin-hydrogel (60.9 ± 1.68%) inhibited melanin formation more effectively than arbutin solution. In addition, arbutin-hydrogel exhibited a more inhibitory impact on L-dopa auto-oxidation (54.90 ± 2.26%) than arbutin solution (38.62 ± 2.26%). In addition, the Wistar rat cutaneous sensitivity testing demonstrated that the hydrogel component did not affect the epidermis. These outcomes demonstrated that the arbutin-hydrogel could potentially be utilized for Arbutin topical delivery, expanding the treatment options for hyperpigmentation disorders.

Lipid-based microemulsion gel for the topical delivery of methotrexate: an optimized, rheologically acceptable formulation with conducive dermatokinetics.

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.

Biofriendly resveratrol loaded glycerosomal nanovesicles improve wound healing in chronic diabetic foot ulcers: In-vitro &in-vivo efficacy evaluation

Chronic diabetic foot ulcers (CDFUs) are complex pathological processes involving persistent inflammation, significantly impacting a patient's quality of life. Resveratrol (RES), recognized for its potent antioxidant and anti-inflammatory properties, faces challenges regarding its permeability. This study aimed to develop Resveratrol glycerosomal nanovesicles (RES-GLY-NVs) for topical application to enhance skin permeation. The optimized formulation was integrated into a 2 % HPMC gel and subjected to comprehensive physicochemical characterization, skin deposition, in vitro release, microbiological, antioxidant, and in vivo assessments. Results revealed RES-GLY-NVs with particle size ranging from 82.19 ± 6.51 nm to 145.70 ± 1.39 nm with PDI less than 0.5, encapsulation efficacy ranging from 89.14 ± 1.39 % to 96.09 ± 2.13 % and a zeta potential ranging from −27.93 ± 6.47 mV to −49.33 ± 1.89 mV. The release profile of RES was obviously ranging from % 54.40 ± 1.71 to 77.47 ± 0.54 % after 8 h. In vitro cell assessment revealed that RES-GLY-NVs have no cytotoxicity on normal cells. The optimized RES-GLY-NVs-HPMC gel displayed pseudoplastic rheological behavior and significantly enhanced RES flux and permeability through excised rat skin compared to plain gel. The In vivo study and histological evaluation of diabetic rats ensured that RES-GLY-NVs-HPMC gel acts as a more effective healing adjunct compared to free RES and conventional therapy. These findings encourage the utilization of RES-GLY-NVs-HPMC gel as a wound-healing drug delivery system in chronic diabetes-related wounds and ulcers.

Development and Evaluation of Acitretin Loaded Solid Lipid Nanoparticles for Topical Drug Delivery System

In order to understand the in vitro drug release of the produced gel, the goal of the current investigation was to construct and characterize. Acitretin loaded Solid Lipid Nanoparticles (ActSLNs). Act SLNs were created utilizing the Box Benhken design and the hot homogenization procedure. Act SLN's average diameter and surface morphology were assessed. Act SLNs were lyophilized, then they underwent stability testing, powder X-Ray diffraction, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared (FT-IR) tests to characterize them. The SLNs were added to a 0.25% w/w Carbopol 940 gel base the Stability study, ex vivo drug release in vitro drug releases in rat skin were carried out. The optimized Act SLNs had a spherical form, an entrapment efficiency of 78.82% to 85.73%, and an average particle size of 123.24nm to 409nm. The generation of SLNs was confirmed by DSC, FTIR, and XRD data. ActSLN gel (0.056mg/cm2) significantly increased the amount of accutane deposited in rat skin compared to Act plain gel (0.012mg/cm2).No discernible change was found in the stability studies, according to stability studies.

Formulation and Evaluation of Invasomal and Ethosomal Gel for Curcumin and Determination of Anti- Fungal Activity

Background: Despite exhibiting anti-inflammatory, antiseptic, and anti-cancer properties, curcumin is not exhibiting the same efficacy as that other non-steroidal anti-inflammatory agents and anti-cancer drugs. The main reason is its poor solubility and poor permeability. To improve the solubility the particle size has to be reduced to the nano level and to improve the permeability vesicular drug delivery approaches have to be adapted. By developing invasomal and ethosomal gels the bioavailability of curcumin can be enhanced. Aim and Objective: The main aim of the study is to develop Invasomal and Ethosomal drug delivery systems for curcumin by various techniques. Methods: Curcumin loaded invasomes were prepared by using a thin film hydration method. Six formulations were prepared by varying drug to lipid ratios (INV1 to INV6). Soya lecithin was used as a phospholipid, span60 was used as a surfactant, limonene was used as terpene, ethanol and chloroform were used as solvents. Curcumin-loaded ethosomes were prepared by using a hot method. Five formulations were prepared by increasing lipid concentration (E1 to E5). Soya lecithin as lipid, propylene glycol, and ethanol as solvent. The prepared formulations were evaluated for particle size, zeta potential, drug content, entrapment efficiency. and in vitro drug release studies. Results: Among all the formulations of Invasomes, INV3 formulation containing a 1:5 ratio of the drug (40 mg) to lipid (200 mg) was considered as best formulation because of its particle size of 327. A total of 1nm, zeta potential of -32.6 mV, highest drug content of 97.5%, entrapment efficiency of 96%, and in vitro drug release of 95% in a time period of 12 hrs. Among all the formulations of ethosomes, the E3 formulation was considered as best formulation due to its particle size of 697.5 nm, zeta potential of - 28.0 Mv, highest drug content of 97.3%, entrapment efficiency of 90%, and in vitro drug release of 94.6% in a time period of 12 hrs. Conclusion: The best invasomal and ethosomal formulations were incorporated into gel and evaluated for pH, viscosity, Spreadability, drug content, in vitro drug release studies, and ex vivo studies. INV3 and E3 were incorporated into gel and comparative studies were made with plain gel. Among the three gels (PG, INV3G, E3G), invasomal gel (INV3) exhibited the highest content drug content of 81%, pH of 6.6, spreadability 14.8g cm/sec, in vitro drug release of 90.6%, ,and ex vivo drug release of 97% in a time period of 12 hrs with the release rate of 32.53 microgram/cm2/hr-1/2, the flux of 0.346 μg/cm2/hr and permeation coefficient of 42.71 cm/hr.

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p &lt; 0.01) after after two hours of the experiment than it had been (p &lt; 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

Design of Hydrogel for the Drug Delivery of Less Permeable Ursolic Acid Isolated from Rhododendron arboreum Flower in Animal Skin Membrane

Ursolic acid (UA) is a pentacyclic triterpene that has antioxidant, anticancer, and anti-inflammatory properties. As it belongs to the biopharmaceutical classification system IV due to its poor water solubility and permeability restricts its use in clinical application. So, the research is focused on the development of hydrogel containing encapsulated liposomes of ursolic acid to increase its permeability. The ursolic acid liposomal gel was prepared with a 0.5%, 1%, and 1.5% mixture of carbopol 934P and HPMC K4M as gelling agents. The pH and spreadability of liposomal gel were found to be in the range of (6.93±0.035 to 7.12±0.03) and (15.41±0.36 to 24.47±0.90) g.cm/sec respectively. The drug content was found to be in (19.77±0.02 to 20.11±0.02)%. The study of drug release kinetics showed Higuchi release followed by a non-Fickian diffusion mechanism. The result of the permeation study by Franz diffusion cell showed 1.55 times higher compared to the plain gel at the 5th hour of the study with a flux value of 0.455(mg/cm2/hr). It resolved the fast and enhanced delivery of liposomal ursolic acid through the skin membrane.

Can silver nanoparticles stabilized by Fenugreek (Trigonella foenm -graecum) improve tibial bone defects repair in rabbits? A preliminary study

Background: A fracture is considered a medical emergency leading to considerable complications. Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits. Methods: AgNPs were reduced with FG, loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis the right tibia in each rabbit. Groups 1 to 4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations. Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0±1.7 nm, and a surface charge of -7.8±0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5±0.2, the viscosity of 4000 and 1875 cPs, and spreadability of 1.6±0.14 and 2.0±0.15 for both FG and AgNPs-FG hydrogel, respectively. Radiographic union scale was significantly (p&lt;0.05) improved in group 2 with significant (P &lt; 0.05) increase of bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4. Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits' tibial bone healing process.

Permeability reduction techniques: Plain and fiber HPAM gels in fractured cores

The aim of this study is to investigate how fibers influence the ability of polymer gels to resist washing out from fractures. For this purpose, synthetic and mineral wool fibers were integrated into polymer gels. These fiber-gels were compared to plain gels using bottle tests, viscosity measurements, and fractured core flooding experiments.The bottle tests show no effect of 13-mm-long synthetic fibers on gel strength. However, inside a constricted fracture, the polymer-synthetic fiber gel exhibited 8.4 times higher resistance to the flow of brine compared to the plain gel. This is explained by the retention of the fibers at the constriction point. In low salinity brine, mineral wool fibers allowed a substantial improvement in gel strength, while, at the same time, a reduction in the concentration of chemicals by 40% was made possible.Furthermore, with the addition of 0.6 wt.% mineral wool fibers, the viscosity of the 0.3 wt.% polymer gel increased from 560.5 to 106,920 cp. In fact, in a 1-mm-wide fracture, a gel containing 0.3 wt.% polymer and 0.6 wt.% mineral wool fiber achieved a post-flush pressure gradient that was 58 times higher than a 0.75 wt.% plain polymer gel. Unfortunately, the choice of a makeup brine with an increased salinity resulted in the deterioration of fiber-gel strength. Nonetheless, a substantial improvement of gel strength can be achieved by adding 0.6 wt.% mineral wool fibers, even if the salinity is as high as 143 g/L. Moreover, in experiments in which the permeability of the adjacent matrix was very low, 0.018 mD, a gel of 0.3 wt.% polymer and 0.6 wt.% mineral wool fiber prepared in 242.6 g/L brine, was still superior to a 0.75 wt.% plain gel prepared in low salinity brine.Experimentation with large fracture widths of 2.55 mm and 4 mm was also done to confirm gel effectiveness. For example, a gel of 0.3 wt.% polymer and 0.6 wt.% mineral wool fiber, prepared in 14 g/L brine, provided a 1.46 times higher post-flush pressure gradient in a 2.55-mm-wide fracture, as compared to that of a 0.75 wt.% plain polymer low salinity gel in a 1-mm-wide fracture. With an increase in the salinity, to 234.6 g/L, of the makeup brine used with a fiber-gel, the resistance to the flow of brine in a 2.55-mm-wide fracture became comparable to that of a plain gel in a 1-mm-wide fracture. In a 4-mm-wide fracture, a gel with 0.3 wt.% polymer prepared in 234.6 g/L brine and one of 0.5 wt.% polymer prepared in 14 g/L brine, each with 0.6 wt.% mineral wool fiber, provided maximal post-flush pressure gradients equal to 12–14 psi/ft. This is the same range usually expected from a 0.5 wt.% relatively low molecular weight plain polymer gel in a 1-mm-wide fracture.Although, fibers improved the ability of gels to resist washing out from fractures, in a 4-mm-wide fracture such a fiber-gel could not provide notable resistance to the flow of brine with an increase in the superficial flow velocity higher than 1,000 ft/d. Discovering formulas that would increase the resistance of gels to being washed out of wide fractures must continue.

Effect of extract gel of Sargassum sp. against histopathological of the number of fibroblast cells in the burn healing process

Introduction: Burns are injuries caused by heat and cause damage to the skin. Burns are characterized by red, peeling skin. Burns must be treated properly so that wound healing can close completely. In Indonesia, seaweed is a promising commodity. From 5.2 million wet tons in 2011 to 9.2 million tons in 2013, seaweed output increased by 76.4 percent in Indonesia. This study aimed to study the histopathological picture of burn tissue given Sargassum sp. Methods: An experimental study design with a randomized post-test-only control group design was used for this study. White mice (Mus musculus), the study's population, made up this group. The study was divided into 4 treatment groups. The results of the calculation of the number of fibroblast cells were then evaluated using statistical tests to determine differences between groups. Data analysis was carried out using SPSS ver. 25 with a One-Way ANOVA test. Results: The mean result of fibroblast cell count in group 1 (plain gel) was 36.14 PLP, group 2 (Sargassum sp. 5%) was 51.28 PLP, group 3 (Sargassum sp. 10%) was 53.36 PLP and group 4 (Sargassum sp. bioplacenton) 20.05 PLP. The results of the statistical test showed that there was a significant difference between groups with a p-value of 0.03 (&lt;0.05). Conclusion: The results of the histology show that there is a potential content of Sargassum sp. to affect wound healing.

Acitretin-loaded nanoethosomal gel for the treatment of psoriasis: Formulation, optimization, in vitro, and in vivo assessment

Acitretin (ACT) is a second-generation systemic retinoid used to treat severe psoriasis. However, its poor aqueous solubility and systemic adverse effects make it impractical for oral administration. The primary objective of this research is to prepare, optimize, and evaluate a nanogel consisting of acitretin-loaded ethosomes (ACT-ETH) for its anti-psoriatic potential. A 32 full factorial design was employed for optimization. Thin-film hydration was adopted to prepare ACT-ETH, and then their physicochemical characteristics were tested. The optimized ACT-ETH was converted into a carbopol gel and then evaluated for cytotoxicity, skin irritation, and anti-psoriatic properties. The vesicle size, zeta potential (ZP), and percent entrapment efficiency (% EE) of the optimal ACT-ETH are 147 ± 2.15 nm, −11.5 ± 0.25 mV, and 90.70 ± 0.89%, respectively. The fluorescence microscopy study has shown that ethosomes may go deeper into the skin layers. Compared to plain gel, ACT-ETH gel greatly increased skin permeability and deposition in the ex-vivo skin permeation and deposition tests. The in vitro cytotoxicity investigation revealed that the cytotoxicity of ACT against normal cells (L-929) was significantly reduced by ACT-ETH gel compared to plain ACT gel. The skin irritation study proved that ACT-ETH gel was well tolerated and safe for use on the skin. The in vivo anti-psoriatic study showed that using ACT-ETH gel to treat psoriasis on the skin led to a significant improvement in the therapeutic response. Based on these results, ACT-ETH gel has the potential to increase the topical anti-psoriatic action of ACT by mitigating its known drawbacks.

Novel Transethosomal Gel Containing Miconazole Nitrate; Development, Characterization, and Enhanced Antifungal Activity.

Miconazole nitrate (MCNR) is a BCS class II antifungal drug with poor water solubility. Although numerous attempts have been made to increase its solubility, formulation researchers struggle with this significant issue. Transethosomes are promising novel nanocarriers for improving the solubility and penetration of drugs that are inadequately soluble and permeable. Thus, the objective of this study was to develop MCNR-loaded transethosomal gel in order to enhance skin permeation and antifungal activity. MCNR-loaded transethosomes (MCNR-TEs) were generated using the thin film hydration method and evaluated for their zeta potential, particle size, polydispersity index, and entrapment efficiency (EE%). SEM, FTIR, and DSC analyses were also done to characterize the optimized formulation of MCNR-TEs (MT-8). The optimized formulation of MCNR-TEs was incorporated into a carbopol 934 gel base to form transethosomal gel (MNTG) that was subjected to ex vivo permeation and drug release studies. In vitro antifungal activity was carried out against Candida albicans through the cup plate technique. An in vivo skin irritation test was also performed on Wistar albino rats. MT-8 displayed smooth spherical transethosomal nanoparticles with the highest EE% (89.93 ± 1.32%), lowest particle size (139.3 ± 1.14 nm), polydispersity index (0.188 ± 0.05), and zeta potential (-18.1 ± 0.10 mV). The release profile of MT-8 displayed an initial burst followed by sustained release, and the release data were best fitted with the Korsmeyer-Peppas model. MCNR-loaded transethosomal gel was stable and showed a non-Newtonian flow. It was found that ex vivo drug permeation of MNTG was 48.76%, which was significantly higher than that of MNPG (plain gel) (p ≤ 0.05) following a 24-h permeation study. The prepared MCNR transethosomal gel exhibited increased antifungal activity, and its safety was proven by the results of an in vivo skin irritation test. Therefore, the developed transethosomal gel can be a proficient drug delivery system via a topical route with enhanced antifungal activity and skin permeability.

Development of kojic acid loaded collagen-chitosan nanoparticle as skin lightener product: in vitro and in vivo assessment

In the present study, an ionic gelation and ultrasonic approach was performed to produce kojic acid (KA) loaded chitosan(CS)/collagen(CN) nanoparticle(NP) (CSCN-NP) which aimed to increase the dermal delivery and anti-pigmentation effect. To optimize the CSCN-NP the effect of the amount of CN was investigated. The results showed that increasing CN from 0 to 500 mg increased the mean particle size and entrapment efficiency of KA-CSCN-NP from 266.07 ± 9.30 nm to 404.23 ± 9.44 nm and 17.37 ± 2.06% to 82.34 ± 2.16%, respectively. Differential scanning calorimetry confirmed the amorphous form of KA in CSCN-NP, while scanning electron microscopy revealed that the nanoparticles were spherical. There was no chemical interaction between KA and the other components base on attenuated total reflectance-Fourier transform infrared spectroscopy. The skin permeability test showed that KA-CSCN-NP gel delivered more KA to the dermal layers (29.16 ± 1.67% or 537.26 ± 537.26 μg/cm2) and receiver compartment (15.04 ± 1.47% or 277.15 ± 27.22 μg/cm2) compared to KA plain gel. In vitro cytotoxicity assay demonstrated that the improved KA-CSCN-NP was non-toxic. Dermal irritating test on Wistar rats showed that the KA gel was non-irritating. Furthermore, KA-CSCN-NP was found to inhibit melanin formation to a greater extent than free KA and significantly inhibited L-dopa auto-oxidation (94.80 ± 2.41%) compared to pure kojic acid solution (75.28 ± 3.22%). The observations of this study revealed that the produced KA-CSCN-NP might be used as a potential nano-vehicle for KA dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.

Quality-by-design-based development of ultradeformable nanovesicular transgelosome of standardized Piper longum extract for melanoma.

Background: Melanoma is the most aggressive and deadly form of skin cancer. The stratum corneum of the skin is a major obstacle to dermal and transdermal drug delivery. Ultradeformable nanovesicular transferosome has the capacity for deeper skin penetration and its incorporation into hydrogel forms a transgelosome that has better skin permeability and patient compliance. Method: Here, the quality-by-design-based development and optimization of nanovesicular transgelosome of standardized Piper longum fruit ethanolic extract (PLFEE) for melanoma therapy are reported. Results: Compared with standardized PLFEE-loaded plain gel, the transgelosome displayed optimal pharmaceutical properties and improved ex vivo skin permeability and in vivo tumor regression in B16F10 melanoma-bearing C57BL/6 mice. Conclusion: The results reflect the potential of transgelosome for melanoma therapy.

Designing and evaluation of dermal targeted combinatorial nanostructured lipid carrier gel loaded with curcumin and resveratrol for accelerating cutaneous wound healing

A nanostructured lipid carrier containing combined curcumin (CUR) and resveratrol (RSV) was prepared and tested for its potential to accelerate wound healing through topical administration. Prepared nano lipid carrier (NLC) formulation had a particle size of 132.3 ± 4.54 nm, polydispersity index (PDI) of 0.478, and zeta potential of −16.6 mV. Entrapment efficiency (EE) for CUR and RSV was found to be 94.21 ± 0.28% and 84.61 ± 0.15%, respectively. Drug loading was found to be 8.560 ± 0.948% (for CUR) and 7.602 ± 0.452% (for RSV). NLC formulation was converted to NLC gel by incorporation of Carbopol 934 for enhancing its dermal applicability. Flux and permeability coefficient for CUR and RSV in NLC gel was found to be 22.087 µg/cm2/h, 11.299 µg/cm2/h, and 0.2208, 0.1129, respectively, through goat ear skin and 19.213 µg/cm2/h, 22.66 µg/cm2/h and 0.1921, 0.2266, respectively, through Strat-MTM membrane. Dermatokinetic study revealed significant enhancement in Cskin max and AUC0–12h in skin sample treated with NLC gel in comparison with plain gel. Also, NLC gel showed longer retention time which indicates prolonged drug action at targeted site thus, NLC gel may show better therapeutic efficacy than plain gel.

Eco-friendly preparation, characterization, evaluation of anti-melanogenesis/antioxidant effect and in vitro/in vivo safety profile of kojic acid loaded niosome as skin lightener preparation

In the current study, an ultrasonic approach (as green method) was utilized to prepared kojic acid niosome (kojisome) which aimed to increase the dermal delivery and improving anti-melanogenesis properties. The study’s findings demonstrated that increasing cholesterol enhanced the mean particle size from 68.333 ± 5.686 nm to 325.000 ± 15.099 nm and entrapment efficiency 0% to 39.341 ± 4.126% of the kojisome. Cholesterol may enhance the number and rigidity of bilayers that induced a size enhancement and entrapment efficiency. The skin permeability test revealed that kojisome gel had more kojic acid in dermal layers (437.563 ± 29.857 μg/cm2 or 16.624 ± 1.379%) than kojic acid plain gel (161.290 ± 14.812 μg/cm2 or 6.128 ± 0.672%). The niosome’s lipophilicity allowed for gradual penetration, possibly due to better contact with the skin layers. Also, the extended-release behavior of improved kojisome exhibited high safety profile and low side effect in In vitro cytotoxicity assay, dermal irritation test, and Histo-pathological evaluation. Furthermore, optimum kojisome inhibited melanin formation (53.093 ± 2.985% at 1000 µM) higher than free kojic acid (62.383 ± 1.958%) significantly (p < 0.05). In addition, Kojisome 6 inhibited L-dopa auto-oxidation greater extent (94.806 ± 2.411%) than pure kojic acid solution (72.953 ± 2.728%). Kojisome by delivering and targeting large amount of kojic acid on specific site causes high efficacy in inhibition of melanin synthesis. The observations of this study revealed that the produced kojisome might be used as a potential nano-vehicle for kojic acid dermal administration, thereby opening up innovative options for the treatment of hyperpigmentation problems.