Irritation Studies Research Articles

Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime

Objectives This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. Methods Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. Results The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential −20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. Conclusion This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Enhancing anti-inflammatory effect of brucine nanohydrogel using rosemary oil: a promising strategy for dermal delivery in arthritic inflammation.

Brucine (BRU), an active constituent of Strychnos nux-vomica L., is one of the potential agents to control subside swelling in arthritis. However, its hydrophobic nature, poor permeation, shorter half-life, narrow therapeutic window, and higher toxicity impede its clinical applications. Hence, this investigation was aimed to develop and evaluate novel BRU loaded β-cyclodextrin (β-CD) nanosponges (BRUNs) hydrogel consisting rosemary essential oil (RO), which have been tailored for delayed release, enhanced skin permeation, and reduced irritation, while retaining anti-oxidant and anti-inflammatory activities of this bioactive. Firstly, BRUNs were fabricated by melt technique and characterized appropriately. BRUNs6 demonstrated twofold enhancement in BRU solubility (441.692 ± 38.674) with minimum particle size (322.966 ± 54.456) having good PDI (0.571 ± 0.091) and zeta potential (-14.633 ± 6.357). In vitro release results demonstrated delayed release of BRU from BRUNs6 (67 ± 4.25%) over 24h through molecular diffusion mechanism. Further, preserved anti-inflammatory (53.343 ± 0.191%) and antioxidant potential (60.269 ± 0.073%) of bioactive was observed in BRUNs6. Hence, this Ns batch was engrossed with Carbopol®934 hydrogel with RO and characterized. In vitro (release and anti-inflammatory activity), ex-vivo (skin permeability) and in vivo (carrageenan-induced inflammation) assays along with irritation study were conducted for fabricated hydrogels. Results revealed that in vitro release of BRU was further delayed from Ns hydrogel with RO (56.45 ± 3.01%) following Fickian mechanism. Considerable enhancement in skin permeability (60.221 ± 0.322µg/cm2/h) and preservation of anti-inflammatory activity (94.736 ± 2.002%) was also observed in BRUNs6 hydrogel containing RO. The irritation of BRU was found reduced (half) after its entrapped in Ns. Further, as a proof of concept, BRUNs6 hydrogel with RO effectively reduced (75.757 ± 0.944%) carrageenan-induced inflammation in rat model in comparison to pure BRU (54.914 ± 1.081%). Hence, BRUNs hydrogel with RO can be considered as a promising alternative for dermal delivery of BRU in arthritis.

Statistical modeling, optimization and characterization of andrographolide loaded emulgel for its therapeutic application on skin cancer through enhancing its skin permeability

Andrographolide is a natural diterpene lactone with multiple biological effects. In the present study, a total of 11 andrographolide-loaded emulgels (ANG 1- ANG 11) were prepared by emulsification and solvent evaporation method using flaxseed oil and xanthan gum in different ratios, as suggested by the Design-Expert software. A 2-factor-5-level design was employed with different responses including spreadability, extrudability, viscosity, and drug release after 1 h (h) and 24 h. Based on the Design-Expert software response, the optimized emulgel ANG 12 was formulated and evaluated. The 24 h In-vitro drug release was found to be 95.7 % following Higuchi kinetics. Ex-vivo skin retention of 784.78 ug/cm2 was observed during the study. MTT assay performed on Human epidermoid carcinoma (A-431) cells demonstrated cell growth arrest at G0/G1 and G2/M phase after 24 h of ANG 12 treatment (IC50: 11.5 µg/ml). The cellular permeability of ANG-12 was assessed by Fluorescein isothiocyanate (FITC) assay. Compared to untreated cells (0.54 % uptake) the ANG-12 treated cells had shown 87.17 % FITC permeation. The biocompatibility study performed on non-cancerous human dermal fibroblast cells (HDF cells) shows 91.54 % viability after 24 h of the treatment showing the non-toxic nature of ANG-12. Confocal imaging had shown a significant time-dependent increase in in-vivo cellular uptake with enhanced, progressive penetration of the emulgel into the skin. An in-vivo skin irritation study conducted on Swiss albino mice confirmed the safety aspects of the ANG 12. Hence, it can be concluded that nanoemulgel of andrographolide (ANG 12) could be a novel approach to treating skin cancer.

A green chemistry approach for preparation of metronidazole-zinc (ІІ) complexes: In vitro characterization, antimicrobial activity and promising cytotoxicity

Antibiotic-metal complexes attract the attention of pharmaceutical scientists who endeavor to increase the activity of antibiotics currently in use as those looking for new compounds possessing modified pharmacological and toxicological properties. This research proposed enhanced antimicrobial and cytotoxic activities of metronidazole and reduced irritancy of zinc chloride through complexation. The chemically green preparation of metronidazole: zinc (ІІ) complexes with different ratios: (A; 2:1), (B; 1:1) and (C; 1:2), revealed the formation of three complexes. The differences between their structures, physical and chemical properties were evaluated using morphological characteristics, DSC, XRD, FTIR, Mass spectrometry, and UV–Vis spectroscopy. The antimicrobial activities of the complexes were increased when compared to the parent drug where complex-C manifested the highest antibacterial activity (MIC = 0.625 mM and 10 mM for the bacterial strains and C. albicans, respectively). The antitumor efficacy of the complexes was studied against HepG2 and MCF-7 human cancer cell lines. Complex-A showed the highest cytotoxicity against HepG2 cells (IC50 = 17.2 μM), while, complex-C displayed the most cytotoxic activity against MCF-7 cells (IC50 = 29.0 μM). The in vivo skin irritancy study of the complexes on rats and their histological examination were assessed and showed no erythema and/or edema. Our results suggest the promising antimicrobial and antitumor activity of the prepared metronidazole-zinc complexes.

Formulation and Assessment of Lipid-based Nanoformulation of Luliconazole

The luliconazole preformulation study aimed to determine the best way to administer medicine using SNEDDS. The plain white powder, luciconazole, showed a number of different crystal structures and was very soluble in isopropyl myristate and oleic acid, as confirmed through partition coefficients in n-octanol. With a robust linear standard curve at 295 nm, UV spectroscopy verified its dependability for analysis. Luliconazole and the necessary excipients for SNEDDS formulation were found to be compatible according to fourier-transform infrared spectroscopy (FTIR) spectra. Using a 32-factorial design enhanced the efficacy and stability of SN-7 batches, especially when diluted with water. Thermal studies revealed formulation dynamics-critical thermal behaviors and crystalline structures (DSC and XRD). The end SNEDDS showed a strong suppression of Candida albicans growth and a higher viscosity, allowing for longer surface retention. Ethical approval facilitated comparative evaluations against a commercial formulation. High-performance liquid chromatography (HPLC) analysis validated SN-7’s purity, enabling a benchmark for monitoring luliconazole plasma concentrations post-application and ex-vivo permeation studies, vital for potential fungal infection treatments. A rigorous three-month stability study affirmed SN-7’s unwavering properties across diverse environmental conditions, ensuring sustained effectiveness. An IEAC-approved skin irritation study on albino wistar rats endorsed SN-7’s minimal irritancy, underscoring its safety and comfort, which is pivotal for pharmaceutical acceptance in topical drug delivery.

QUALITY BY DESIGN SUPPORTED CONSTRUCTION OF ORAL FAST-DISSOLVING FILMS FOR TELMISARTAN: RECONNOITERING THE QUALITY ATTRIBUTES

Objective: The angiotensin II receptor antagonist telmisartan (TMS) is often used to treat hypertension. The BCS class II antihypertensive drug TMS has a low solubility, poorly absorbed when taken orally. The goal of this study was to formulate an oral fast-dissolving film (OFDF) of TMS. In recent years, the concept of a rapidly dissolving dosage form as an innovative delivery system has gained popularity. By decreasing dosing frequency, maximize therapeutic effectiveness, bioavailability, and stability. It will also prevent the drugs from being metabolized in the first place. This technique allows for faster drug absorption from the gastrointestinal tract (GIT), which might result in a more rapid onset of action. Methods: An experimental design known as Box-Behnken was employed to optimize a OFDF. Mango kernel (100-300 mg), maltodextrin (200-350 mg), and propylene glycol (PG) (15-30%) were chosen as independent variables with the highest preference. Included measurements of T5 tensile strength, disintegration time, folding endurance, elongation, and drug release efficiency as dependent variables. Results: The physical properties of the films were found to be satisfactory, and Fourier transform infrared (FTIR) analysis failed to detect any drug-polymer interaction. F4 was found to have the greatest bioadhesive strength of 49.82 gm and the longest ex-vivo mucoadhesion duration of 189 min. A higher concentration of mango kernel in the formulation resulted in a greater rate of drug release. More than 60% of the drug was discharged within 10 min. Conclusion: The oral mucosa of a rat was used for ex-vivo for irritation studies. Based on the pharmacokinetic plasma parameters, which is made into quick-dissolving films that are taken by mouth, is much better absorbed than aqueous suspensions. Studies of the enhanced formulation's stability showed that F4 may be stored for up to three months without deterioration.

DEVELOPMENT AND EVALUATION OF NANOBIOCOMPOSITE TOPICAL FORMULATION

Objective: The proposed research involving transferosomes within a hydrogel matrix offers a promising approach for enhanced wound healing. This system aims to facilitate the dermal delivery of nanosized curcumin while incorporating Ascorbic acid and Salicylic acid. The integration of these components holds the potential for advancing chronic wound therapy. Methods: Curcumin transferosomes were formulated by the lipid thin film hydration method and further optimization was carried out using 32 full factorial design. The transferosome formulation, prepared using phospholipon 90G, involved selecting specific variables: the quantity of edge activator and sonication duration as independent factors, while the optimization process considered particle size and entrapment efficiency as dependent variables. Following the optimization of the transferosomes, a hydrogel formulation was developed using the central composite design approach. Results: Optimized transferosome (Batch F8) showed 87.75±3.74 nm (nanometer) particle size and 91.18±2.71% entrapment efficiency. Hydrogel was formulated by Central composite design, selecting pH and spreadability as dependent factors, to which was added curcumin transferosomes, Ascorbic acid and Salicylic acid. The data was analyzed using Stat-ease Design-Expert v7.0.0 software. The optimized batch F3 showed a pH of 6.84, spreadability of 12.89 gm. cm/sec and Curcumin release of 87.47%. Drug release from nanobiocomposite hydrogel was evaluated using the in vitro study of the formulation. The various kinetic models were applied to in vitro release data for the prediction of the drug release kinetic mechanism. The release constants were calculated from the slope of appropriate plots, and the regression coefficient (R2) was determined. It was found that the in vitro drug release of the formulation was best explained by Higuchi as the plots show the highest linearity. The regression coefficient (R2) was found to be 0.907, 0.9266 and 0.9536 for Ascorbic acid, Salicylic acid and Curcumin, respectively. Conclusion: The nanobiocomposite topical formulation was thus prepared, tested and for skin irritancy study. There is no noticeable signs of erythema, edema, or inflammation were observed on the skin. These results indicate that the developed transdermal formulation does not cause skin irritation and can be considered non-irritating.

Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ.

Aims: Thisstudy was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved athin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generateERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with anenhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.

Cationized gelatin-sodium alginate polyelectrolyte nanoparticles encapsulating moxifloxacin as an eye drop to treat bacterial keratitis

A mucoadhesive polyelectrolyte complex (PEC) nanoparticles were developed for ocular moxifloxacin (Mox) delivery in Bacterial Keratitis (BK). Moxifloxacin-loaded G/CG-Alg NPs were prepared by an amalgamation of cationic polymers (gelatin (G)/cationized gelatin (CG)), and anionic polymer (sodium alginate (Alg)) along with Mox respectively. Mox@CG-Alg NPs were characterized for physicochemical parameters such as particle size (DLS technique), morphology (SEM analysis), DSC, XRD, encapsulation efficiency, drug loading, mucoadhesive study (by texture analyzer), mucin turbidity, and viscosity assessment. The NPs uptake and toxicity of the formulation were analyzed in the Human Corneal Epithelial (HCE) cell line and an ocular irritation study was performed on the HET-CAM. The results indicated that the CG-Alg NPs, with optimal size (217.2 ± 4 nm) and polydispersity (0.22 ± 0.05), have shown high cellular uptake in monolayer and spheroids of HCE. The drug-loaded formulation displayed mucoadhesiveness, trans-corneal permeation, and sustained the release of the Mox. The anti-bacterial efficacy studied on planktonic bacteria/biofilms of P. aeruginosa and S. aureus (in vitro) indicated that the Mox@CG-Alg NPs displayed low MIC, higher zone of bacterial growth inhibition, and cell death compared to free Mox. A significant reduction of bacterial load was observed in the BK-induced mouse model.

Sensory irritation and use of the best available science in setting exposure limits: Issues raised by a scientific panel review of formaldehyde human research studies

As a high production volume chemical with recognized sensory irritation and widespread exposure, the human health risk potential of formaldehyde has been reviewed by many international regulatory agencies and scientific advisory bodies. A scientific panel, the Human Studies Review Board, under the auspices of the EPA's Toxic Substances Control Act (TSCA) program recently reviewed the sensory irritation studies included in the 2022 Draft Integrated Risk Information System (IRIS) Formaldehyde Hazard Assessment in the context of their use in a weight of evidence evaluation of acute inhalation health effects. This panel issued a series of recommendations on the use of these studies for the purposes of calculating exposure limits (e.g., study design preferences; uncertainty adjustment). Considering that these recommendations might reflect topic areas with varying degrees of scientific consensus, this commentary reflects on commonalities and distinctions amongst international formaldehyde exposure limits based on sensory irritation. Notably, each review panel charged with an assessment of the science recommended that no adjustment was needed to account for either exposure duration or human variability. These areas of scientific consensus should be considered as the best available science for the purposes of setting exposure limits in the anticipated TSCA Risk Evaluation on formaldehyde.

Enhanced in vitro and ex vivo transdermal permeation of microemulsion gel of tapentadol hydrochloride

Aim of the current study is to develop a microemulsion gel for transdermal delivery of tapentadol hydrochloride. Microemulsion was developed using phase diagram and subjected to assay, globule size, PDI, zeta potential, TEM and in vitro drug release studies. The optimized microemulsion was converted into gel using carbopol 934 NF and evaluated for viscosity, spreadability, in vitro, ex vivo, FTIR, DSC, stability and skin irritation studies. The mean globule size, PDI, zeta potential and in vitro drug release of microemulsion were found 247.3 nm, 0.298, –17.6 mV and 98.42% respectively. In vitro and ex vivo drug release of gel was found 92.2% and 88.6% in 24 h. Viscosity and spreadability results indicated ease of application and no incompatibility was observed from FTIR studies. The skin irritation studies showed absence of erythema. Key findings from the current research concluded that microemulsion gel was suitable for effective transdermal delivery.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) invitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. ZER demonstrated significant potential as a skin-lightening agent.

Co-delivery of Brinzolamide and Timolol from Micelles-laden Contact Lenses: In vitro and In Vivo Evaluation.

Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 μL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.

A nine-month repeat-dose intravaginal ring (Ovaprene) irritation study in sheep

ObjectivesOvaprene is a novel, investigational, intravaginal hormone-free monthly ring contraceptive designed for use in women of reproductive age to be worn over multiple weeks (one menstrual cycle). The objective of this work was to evaluate the safety of Ovaprene during a nine-month repeat-dose sheep study. Study designIn addition to traditional safety endpoints such as histopathological evaluation of the sheep female reproductive tract, vaginal fluids were collected and tested for released iron over time. Also, the amount of iron in the rings was assessed following removal, and serum iron levels were measured. There were four sheep in each group (Ovaprene group and sham group). ResultsThere were no macroscopic clinical findings. There was minimal to mild, mixed or mononuclear cell infiltration present in all levels of vagina (cranial, mid, and caudal) from all animals including sham controls based on post-study necropsy. The female reproductive tract from animals treated with the Ovaprene ring was comparable to the sham controls. The concentrations of serum iron in sheep treated with Ovaprene ring were similar compared to a sham treated animal. The average amount of ferrous gluconate released from Ovaprene over the 29-day period of use was 175 mg of the approximately 512 mg nominally loaded into the rings. ConclusionsOverall, the Ovaprene devices were well-tolerated in female sheep. ImplicationsThis study should support a chronic (e.g., one year) contraceptive efficacy study in women.

Fabrication, Optimization, and Evaluation of Transdermal Patch: As an Alternative and Effective Transdermal Delivery System for Nebivolol HCl.

Nebivolol HCl is a unique third-generation beta blocker that has less oral bioavailability and exhibits various adverse effects like gastrointestinal disturbance and abdominal pain. This study aimed to formulate and evaluate nebivolol HCl transferosomal transdermal patches to reduce the problems associated with oral delivery of the drug and enhancement of drug permeation through the skin. Nebivolol HCl loaded transferosomes were prepared by thin film hydration method. Eight formulations were prepared based on the two independent variables, type of surfactant (Tween 80 and Span 80) and Phospholipid: Edge activator ratio and were evaluated for their vesicle size, PDI, and entrapment efficiency. The optimized formulations were incorporated into transdermal patches, which were evaluated for physicochemical properties, in-vitro and ex-vivo permeation, skin irritancy, and stability studies. The vesicle size of the transferosomes ranged from 49nm to 93nm, and EE% varied from 39% to 79%. Vesicles formed with Span 80 as an edge activator showed smaller vesicle size and greater EE% as compared to Tween 80. Based on the results, TW4 and SP4 were selected as the optimized formulations for further incorporation into the transdermal patches. In-vitro and ex-vivo permeation studies showed permeation in the order F2 > F3 > F1, indicating that transferosomal formulations showed superior permeation of the drug compared to plain Nebivolol HCl patches. Span 80 transferosomes showed a slightly better permeation than Tween 80. Stability studies showed that transferosomes and the transdermal patches demonstrated good stability under proper storage conditions. The study concluded that transferosomal patches of Nebivolol HCl could be used as a potential approach with effective transdermal delivery for the management of hypertension.

Development of Curcumin and Turmerone Loaded Solid Lipid Nanoparticle for Topical Delivery: Optimization, Characterization and Skin Irritation Evaluation with 3D Tissue Model.

Curcuma longa L., commonly known as turmeric, is renowned for its therapeutic benefits attributed to bioactive compounds, namely curcumin (Cur) and aromatic turmerone (Tur), present in its rhizome. These compounds exhibit diverse therapeutic properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, the topical application of these compounds has a significant potential for inducing skin irritation. This study focuses on formulating solid lipid nanoparticle (SLN) carriers encapsulating both Cur and Tur for reduced irritation and enhanced stability. SLN formulations were prepared by a method using homogenization followed by ultrasonication procedures and optimized by applying response surface methodology (RSM). The optimized SLN formulation demonstrated entrapment efficiencies, with 77.21 ± 4.28% for Cur and 75.12 ± 2.51% for Tur. A size distribution of 292.11 ± 9.43 nm was obtained, which was confirmed to be a spherical and uniform shape via environmental scanning electron microscopy (ESEM) images. The in vitro release study indicated cumulative releases of 71.32 ± 3.73% for Cur and 67.23 ± 1.64% for Tur after 24 hours under sink conditions. Physical stability tests confirmed the stability of formulation, allowing storage at 4°C for a minimum of 60 days. Notably, in vitro skin irritation studies, utilizing the reconstructed human epidermal model (EPI-200-SIT), revealed a significant reduction in irritation with the SLN containing Cur and Tur compared to nonencapsulated Cur and Tur. These findings collectively endorse the optimized SLN formulation as a favorable delivery system for Cur and Tur in diverse topical uses, offering enhanced stability, controlled release and reduced irritation.

Formulation and evaluation of itraconazole-loaded nanoemulgel for efficient topical delivery to treat fungal infections.

Aim: The clinical application of conventional oral dosage form of itraconazole is limited due to its poor bioavailability. The aim of the study was to develop nanoemulgel of Itraconazole for topical delivery. Method: Nanoemulsions were prepared, optimized and further incorporated into a gel and evaluated for homogeneity, pH, viscosity, spreadability, in vitro drug release and skin irritation studies. Results: Cumulative drug release from nanoemulsions was within the range of 37.24 to 47.63% at 10h. Drug release % for all the nanoemulgel formulations at10h was 32.39, 39.75and 45.9% respectively. Nanoemulgel was non-irritant as demonstrated by skin irritation studies in animals. Conclusion: Itraconazole nanoemulgels were proved to be potential for effective topical delivery of drug with enhanced bioavailability.

Development and assessment of rutin loaded transfersomes to improve ex vivo membrane permeability and in vitro efficacy

The melanoma is the most dangerous kind of skin cancer begins in the melanocytes, or cells that make melanin, the pigment that gives your skin its color. Due to the need of local effect topical administration of anticancer drugs could be the best option for clinical therapy. Present study aimed to formulate transfersomes to enhance the skin penetration of rutin (Rtn). Rutin loaded transfersomes (RtnTFs) were formulated by employing central composite design (CCD) of experiment and comprising of various ratios of phospholipid 90H and sodium deoxycholate as independent variables. The assessment of critical parameters suggested higher encapsulation of Rtn and improved stability of formulation with significant drug release (P < 0.05). The RtnTFs shows higher cell inhibition on Murine skin Melanoma cell line (B16–F10). Further, formulated RtnTFs were incorporated in transdermal patches (TPs) to enhance skin deposition. However the higher deposition of about 0.921 ± 0.23 mg/cm3 of Rtn was observed. RtnTFs-TPs exhibited ideal morphological characteristics in scanning electron microscopic images. Ex-vivo skin diffusion studies revealed the sustained release of about 98 ± 0.26 % drug at the end of 36 h (P < 0.05). Skin irritancy study demonstrated the suitability of RtnTFs-TPs for dermal delivery and with higher stability. Hence the topical delivery with delayed release of drug by enhancing the solubility could be the promising strategy for efficient delivery of anticancer agents.

An Integrated Computational and Experimental Approach to Formulate Tamanu Oil Bigels as Anti-Scarring Agent.

Tamanu oil has traditionally been used to treat various skin problems. The oil has wound-healing and skin-regenerating capabilities and encourages the growth of new skin cells, all of which are helpful for fading scars and hyperpigmentation, as well as promoting an all-around glow. The strong nutty odor and high viscosity are the major disadvantages associated with its application. The aim of this study was to create bigels using tamanu oil for its anti-scarring properties and predict the possible mechanism of action through the help of molecular docking studies. In silico studies were performed to analyze the binding affinity of the protein with the drug, and the anti-scarring activity was established using a full-thickness excision wound model. In silico studies revealed that the components inophyllum C, 4-norlanosta-17(20),24-diene-11,16-diol-21-oic acid, 3-oxo-16,21-lactone, calanolide A, and calophyllolide had docking scores of -11.3 kcal/mol, -11.1 kcal/mol, -9.8 kcal/mol, and -8.6 kcal/mol, respectively, with the cytokine TGF-β1 receptor. Bigels were prepared with tamanu oil ranging from 5 to 20% along with micronized xanthan gum and evaluated for their pH, viscosity, and spreadability. An acute dermal irritation study in rabbits showed no irritation, erythema, eschar, or edema. In vivo excisional wound-healing studies performed on Wistar rats and subsequent histopathological studies showed that bigels had better healing properties when compared to the commercial formulation (MurivennaTM oil). This study substantiates the wound-healing and scar reduction potential of tamanu oil bigels.

Formulation and Evaluation of Biopolymer Incorporated Nanogel of Nabumetone

ABSTRACT: The objective of this research was to improve the solubilization, dissolution rate, and thereby anti-inflammatory activity of the BCS class II drug Nabumetone (NSAID). A solid dispersion (SD) approach with Gelucire 50/13 was used to enhance the solubility. Microwave-induced fusion method was used for the development of SD, as it demonstrated a remarkable increase in the solubility and dissolution rate of pure drugs when compared to traditional solid dispersions. A number of parameters of the SD were evaluated in vitro, including solubility, dissolution, and Fourier Transformed Infrared Spectra obtained (FT-IR). The rate of dissolution was inclined to betterment with the drug: polymer ratio 1:0.5 showing drug release 99.60 ± 29. The objective of the work was to evolve a Nanogel for topical delivery of Nabumetone. The emulsification-diffusion method was used to create nanogel using the polymers Carbopol-940, Gelucire-50/13, and triethanolamine as gelling agents. Chitosan was added to the formulation as a biopolymer. Menthol was employed as a penetration enhancer. Using the spontaneous emulsification-diffusion method, six distinct formulations of Nabumetone-loaded Nanogel were successfully created and evaluated for particle size, zeta potential, thermodynamic stability, and rheology study. Using a cellophane membrane, the gels were examined for diffusion study further, and drug content, viscosity, spreadability, pH, and clarity were accessed. The formulation F4 batch had the best in-vitro drug release profile, with a 96.04% release rate over 270 minutes. Optimized gel F4 underwent a skin irritation study on Wistar rats and passed the test. The topical application of Nabumetone as Nanogel proved to be an effective approach to drug delivery.