QbD-Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture.

Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)-loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa-nHA-GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box-Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, -20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine-B loaded nHA-GLT NPs demonstrates considerably higher cellular uptake by the murine-derived macrophages than free rhodamine-B solution. In vitro, cell-based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD-based approach has successfully led to the development of Tofa-nHA-GLT NPs with the potential to target inflamed arthritic joint.

In vitro and in vivo characterization of Miconazole Nitrate loaded transethosomes for the treatment of Cutaneous Candidiasis.

This study aimed to fabricate Miconazole Nitrate transethosomes (MCZN TESs) embedded in chitosan-based gel for the topical treatment of Cutaneous Candidiasis. A thin film hydration method was employed to formulate MCZN TESs. The prepared MCZN TESs were optimized and analyzed for their physicochemical properties including particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (%EE), Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), deformability, and Transmission electron microscopy (TEM). In vitro release, skin permeation and deposition, skin irritation, antifungal assay, and in vivo efficacy against infected rats were evaluated. The optimized MCZN TESs showed PS of 224.8 ± 5.1 nm, ZP 21.1 ± 1.10 mV, PDI 0.207 ± 0.009, and % EE 94.12 ± 0.101 % with sustained drug release profile. Moreover, MCZN TESs Gel exhibited desirable pH, spreadability, and viscosity. Notably, the penetration and deposition capabilities of MCZN TESs Gel showed a 4-fold enhancement compared to MCZN TESs. Importantly, in vitro antifungal assay elaborated MCZN TESs Gel anti-fungal activity was 2.38-fold more compared to MCZN Gel. In vivo, studies showed a 1.5 times reduction in the duration of treatment MCZN TESs Gel treated animal group. Therefore, studies demonstrated that MCZN TESs could be a suitable drug delivery system with higher penetration and good antifungal potential.

Design and Evaluation of Continentalic Acid Encapsulated Transfersomal Gel and Profiling of its Anti-arthritis Activity.

Rheumatoid arthritis restricts the physical ability of patients and increases the disease burden; therefore, research has always been focused on evaluating better therapeutic options. The present research aimed to design Continentalic acid (CA)-loaded transfersomes (CA-TF) embedded in Carbopol gel containing permeation enhancer (PE) for the treatment of rheumatoid arthritis. CA-TF was developed via a modified thin film hydration method and incorporated into Carbopol 934 gel containing Eucalyptus oil (EO) as PE. The fabricated CA-TF showed particle size of < 140 nm with spherical geometry, optimal encapsulation efficiency (EE), and sustained drug release pattern. CA-TF-gel along with PE (CA-TF-PE-gel) showed better ex vivo skin penetration than plain CA gel and CA-TF-gel without PE. In vivo evaluation supported improved therapeutic outcomes of CA-TF-PE-gel in terms of behavioral findings, arthritic index, and histological findings whereas biochemical assays and pro-inflammatory cytokines (TNF-α and IL-1ß) showed a significant decrease in their levels. Furthermore, immunohistochemistry assay for Nrf2 and HO-1 signaling pathways showed significant improvement in the expression of the Nrf2, and HO-1 proteins to depict improvement in arthritic condition in the animal model. CA-TF-PE-gel significantly delivered CA to the diseased target site via a topical route with promising therapeutic outcomes displayed in the CFA-induced arthritic model.

ZnO-NPs embedded biodegradable thiolated bandage for postoperative surgical site infection: In vitro and in vivo evaluation.

Post-operative surgical site infections (SSI) present a serious threat and may lead to complications. Currently available dressings for SSI lack mucoadhesion, safety, efficacy and most importantly patient compliance. We aimed to address these concerns by developing a bioactive thiolated chitosan-alginate bandage embedded with zinc oxide nanoparticles (ZnO-NPs) for localized topical treatment of SSI. The FTIR, XRD, DSC and TGA of bandage confirmed the compatibility of ingredients and modifications made. The porosity, swelling index and lysozyme degradation showed good properties for wound healing and biodegradation. Moreover, in-vitro antibacterial activity showed higher bactericidal effect as compared to ZnO-NPs free bandage. In-vivo wound healing in murine model showed significant improved tissue generation and speedy wound healing as compared to positive and negative controls. Over all, thiolated bandage showed potential as an advanced therapeutic agent for treating surgical site infections, meeting the required features of an ideal surgical dressing.

Mannosylated thiolated paromomycin-loaded PLGA nanoparticles for the oral therapy of visceral leishmaniasis.

AIM: The present study evaluates the efficacy of paromomycin (PM)-loaded mannosylated thiomeric nanoparticles for the targeted delivery to pathological organs for the oral therapy of visceral leishmaniasis. MATERIALS & METHODS: Mannosylated thiolated chitosan (MTC)-coated PM-loaded PLGA nanoparticles (MTC-PLGA-PM) were synthesized and evaluated for morphology, drug release, permeation enhancing and antileishmanial potential. RESULTS: MTC-PLGA-PM were spherical in shape with a size of 391.24 ± 6.91 nm and an encapsulation efficiency of 67.16 ± 14%. Ex vivo permeation indicated 12.73-fold higher permeation of PM with MTC-PLGA-PM against the free PM. Flow cytometry indicated enhanced macrophage uptake and parasite killing in Leishmania donovani infected macrophage model. In vitro antileishmanial activity indicated 36-fold lower IC50 for MTC-PLGA-PM as compared with PM. The in vivo studies indicated 3.6-fold reduced parasitic burden in the L. donovani infected BALB/c mice model. CONCLUSION: The results encouraged the concept of MTC-PLGA-PM nanoparticles as promising strategy for visceral leishmaniasis.