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.

Fabrication and in vitro evaluation of chitosan-gelatin based aceclofenac loaded scaffold.

Scaffold development is a nascent field in drug development. The scaffolds mimic the innate microenvironment of the body. The goal of this study was to formulate a biocompatible and biodegradable scaffold, loaded with an analgesic drug, aceclofenac (Ace). The bioscaffold is aimed to have optimum mechanical strength and rheology, with drug released in a sustained manner. It was prepared via chemical cross-linking method: a chitosan (CS) solution was prepared and loaded with Ace; gelatin (GEL) was added and the mixture was cross-linked to get a hydrogel. 20 formulations were prepared to optimize different parameters including the stirring speed, drug injection rate and crosslinker volume. The optimal formulation was selected based on the viscosity, drug solubility, homogeneity, porosity and swelling index. A very high porosity and swelling index were attained. In vitro release data showed sustained drug delivery, with effective release at physiological and slightly acidic pH. SEM analysis revealed a homogeneous microstructure with highly interconnected pores within an extended polymer matrix. FT-IR spectra confirmed the absence of polymer-drug interactions, XRD provided evidences for efficient drug entrapment within the scaffold. Rheological analysis corroborated the scaffold injectability. Mathematical models were applied to in-vitro data, and the best fit was attained with Korsmeyer-Peppas.

In Vitro and Ex Vivo Evaluation of Fluocinolone Acetonide-Acitretin-Coloaded Nanostructured Lipid Carriers for Topical Treatment of Psoriasis.

Psoriasis is chronic autoimmune disease that affects 2-5% of the global population. Fluocinolone acetonide (FLU) and acitretin (ACT) are widely used antipsoriatic drugs that belong to BCS classes II and IV, respectively. FLU exhibits side effects, such as skin irritation and a burning sensation. ACT also shows adverse effects, such as gingivitis, teratogenic effects and xerophthalmia. In the present study, topical nanostructured lipid carriers (NLCs) were fabricated to reduce the side effects and enhance the therapeutic efficacy. FLU-ACT-coloaded NLCs were prepared by the modified microemulsion method and optimized by the Box-Behnken model of Design Expert® version 12. The optimization was based on the particle size (PS), zeta potential (ZP) and percentage of encapsulation efficiency (%EE). The physicochemical analyses were performed by TEM, FTIR, XRD and DSC to assess the morphology, chemical interactions between excipients, crystallinity and thermal behavior of the optimized FLU-ACT-coloaded NLCs. The FLU-ACT-coloaded NLCs were successfully loaded into gel and characterized appropriately. The dialysis bag method and Franz diffusion cells were used for the in vitro release and ex vivo permeation studies, respectively. The optimized FLU-ACT-coloaded NLCs had the desired particle size of 288.2 ± 2.3 nm, ZP of -34.2 ± 1.0 mV and %EE values of 81.6 ± 1.1% for ACT and 75 ± 1.3% for FLU. The TEM results confirmed the spherical morphology, while the FTIR results showed the absence of chemical interactions of any type among the ingredients of the FLU-ACT-coloaded NLCs. The XRD and DSC analyses confirmed the amorphous nature and thermal behavior. The in vitro study showed the sustained release of the FLU and ACT from the optimized FLU-ACT-coloaded NLCs and FLU-ACT-coloaded NLC gel compared with the FLU-ACT suspension and conventional gel. The ex vivo study confirmed the minimal permeation of both drugs from the FLU-ACT-coloaded NLC gel.

Designing, Optimization and Characterization of Trifluralin Transfersomal Gel to Passively Target Cutaneous Leishmaniasis.

Herein, Trifluralin (TFL) laden transfersomes (TFS) were investigated against Cutaneous Leishmaniasis (CL), via localized and targeted dermal delivery of TFL. Designed TFL-TFS were optimized utilizing 23 full factorial design on the basis of desired response factors including Particle size (P.S), Polydispersity index (PDI), TFL entrapment (%EE) and deformability index (DI). Optimized formulation was found to display P.S of 140.3 ± 2.3, PDI of 0.006 ± 0.002, %EE of 86 ± 0.5 and 43.5 ± 1.0 DI. Results of TEM and XRD analysis have shown intact spherical structure of TFL-TFS and alteration in TFL crystallinity, respectively. Moreover, the optimized TFL-TFS were loaded in Carbopol-940 gel to attain protracted skin retention. TFL-TFS were found to exhibit sustain TFL release profile for up to 24 h. Ameliorated skin permeation of TFL-TFS, even in absence of permeation enhancers, has shown its suitability for cutaneous application. Macrophage uptake assay demonstrated higher intracellular penetration, evidenced by intense reddish fluorescence of rhodamine loaded TFS in comparison to rhodamine-solution. In vitro anti-leishmanial assessment was showing 2.86-folds and 3.07-folds decrement in IC50-value of TFL-TFS against L. tropica KWH23 amastigotes and promastigotes, respectively. Percent inhibition assay against intra-macrophage amastigotes demonstrated that 90.87% amastigotes were assassinated at 50 µg/ml concentration of TFL-TFS, in comparison to the plain TFL-solution, exhibiting 54% parasitic killing.