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• W4309552010 endingPage "104005" @default.
• W4309552010 startingPage "104005" @default.
• W4309552010 abstract "Topical drug delivery against cutaneous leishmaniasis (CL) serves as an effective alternate approach to improve efficacy and reduce systemic adverse effects. The purpose of this study was to develop and investigate the potential of rifampicin and pentamidine co-loaded polymeric nanoparticles (RIF-PTM-PNP) for targeting the Leishmania infected macrophages and its effective antileishmanial therapy. RIF-PTM-PNP were prepared by modified ionic gelation method, trailed by their incorporation into 1% Carbopol gel to prepare RIF-PTM-PNP-Gel. The gel was formulated to ensure the retention of PNP on skin for extended period of time. Formulations were statistically optimized via Box-Behnken design (BBD) based on their particle size (P.S), zeta potential (Z.P) and percent entrapment efficiency (%EE). The optimized RIF-PTM-PNP formulation was further assessed for surface morphology and components compatibility via transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR), respectively. Similarly, RIF-PTM-PNP-Gel was evaluated for physiochemical and rheological attributes. In-vitro drug release profile of RIF-PTM-PNP was determined and compared with RIF-Solution, PTM-Solution and RIF-PTM-PNP-Gel. Moreover, ex-vivo permeation analysis of all the test groups were performed to check their permeation profiles. The in-vitro antileishmanial assay, ex-vivo cell uptake, cell viability and cell toxicity studies of the developed formulations were also accomplished. The optimized formulation indicated suitable particle properties including, 163.1 nm P.S, 0.296 PDI, +29.7 mV Z.P and drug entrapment of RIF (89.10%) and PTM (79.31%), respectively. FTIR analysis showed no interactions between components of RIF-PTM-PNP. Moreover, RIF-PTM-PNP-Gel was homogeneous, has optimal pH with desirable viscosity. The in-vitro release of RIF and PTM from RIF-PTM-PNP and RIF-PTM-PNP-Gel showed more sustained release behavior as compared to RIF and PTM solutions. Similarly, significantly higher skin penetration was observed in case of RIF-PTM-PNP and RIF-PTM-PNP-Gel, when compared with conventional gel. Additionally, RIF-PTM-PNP showed superior percent inhibition, higher macrophage uptake and lower IC50 value against promastigotes in association with drugs solutions. Furthermore, in-vivo skin irritation and histopathology study indicated a safe and non-irritant behavior of the RIF-PTM-PNP-Gel, when compared with 0.8% formalin. Also, the optimized formulation (RIF-PTM-PNP) was found stable for at least 6 months. These findings suggested the successful preparation of co-loaded RIF-PTM-PNP and their incorporation into Carbopol-based RIF-PTM-PNP-Gel for topical administration with sustained drug release, enhanced skin permeation, macrophage uptake and improved antileishmanial effect." @default.
• W4309552010 created "2022-11-28" @default.
• W4309552010 creator A5011430977 @default.
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• W4309552010 date "2023-01-01" @default.
• W4309552010 modified "2023-10-06" @default.
• W4309552010 title "Statistical optimization of co-loaded rifampicin and pentamidine polymeric nanoparticles for the treatment of cutaneous leishmaniasis" @default.
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