Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.

Coalition of Biological Agent (Melatonin) With Chemotherapeutic Agent (Amphotericin B) for Combating Visceral Leishmaniasis via Oral Administration of Modified Solid Lipid Nanoparticles.

In this study, 2-hydroxypropyl-ß-cyclodextrin (HPßCD) grafted solid lipid nanoparticle (SLN)-based bioconjugate was synthesized and used for administering a combination of melatonin (Mel) and amphotericin B (AmB) orally for effective visceral leishmaniasis (VL) treatment. The formulations (HPCD-Mel-AmB SLN) were synthesized by the emulsion solvent evaporation method. HPCD-Mel-AmB SLN showed a high loading capacity and a high entrapment efficiency of AmB (% DL = 9.0 ± 0.55 and % EE = 87.9 ± 0.57) and Mel (% DL = 7.5 ± 0.51 and % EE = 63 ± 6.24). The cumulative percent release of AmB and Mel was 66.10 and 73.06%, respectively, up to 72 h. Time-dependent cellular uptake was noticed for HPCD-Mel-AmB SLN for 4 h. Further, HPCD-Mel-AmB SLN did not show any toxic effects on J774A.1 macrophages and Swiss albino mice. HPCD-Mel-AmB SLN (10 mg/kg ×5 days, p.o.) has significantly diminished (98.89%) the intracellular parasite load in liver tissues of L. donovani-infected BALB/c mice, subsequently highlighting the role of melatonin toward an effective strategy in combating leishmanial infection. Therefore, these results indicated that administration of HPCD-Mel-AmB SLN improve the therapeutic index of the first-line drug in addition to the introduction of biological agent and would be a promising therapeutic candidate for effective VL therapy. In the present study, the objective is to test the efficacy of the chemotherapeutic approach in combination with a biological immunomodulatory agent against leishmanial infection using in vitro and in vivo studies. This information suggests that melatonin could be an efficacious and potent antileishmanial agent.

Hijacking the intrinsic vitamin B12 pathway for the oral delivery of nanoparticles, resulting in enhanced in vivo anti-leishmanial activity.

Surface-functionalized vitamin B12 (VB12) biocompatible nanoparticles exploit the well-characterized uptake pathway of VB12, shielding it from enzymatic degradation and inadequate absorption. In this perspective, subsequent to escalated mucus interaction and diffusion analysis, the nanoparticles were investigated by immunostaining with the anti-CD320 antibody, and their internalization mechanisms were examined by selectively blocking specific uptake processes. It was observed that their internalization occurred via an energy-dependent clathrin-mediated mechanism, simultaneously highlighting their remarkable ability to bypass the P-glycoprotein efflux. In particular, the synthesized nanoparticles were evaluated for their cytocompatibility by analyzing cellular proliferation, membrane viscoelasticity, and fluidity by fluorescence recovery after photobleaching and oxidative-stress detection, making them well-suited for successful translation to a clinical setup. Our previous in vitro antileishmanial results were paramount for their further in vivo and toxicity analysis, demonstrating their targeted therapeutic efficiency. The augmented surface hydrophilicity, which is attributed to VB12, and monomerization of amphotericin B in the lipid core strengthened the oral bioavailability and stability of the nanoparticles, as evidenced by the fluorescence resonance energy transfer analysis.