Showing papers by "Padma V. Devarajan published in 2018"
TL;DR: The high efficacy with significantly reduced dose and a single administration with single shot therapy suggest ART‐LUM P‐LLCPr as a promising new patient friendly alternative for antimalarial therapy.
21 citations
TL;DR: The repeated dose 28-day oral toxicity study demonstrated the safety of the nanocarrier and reduced hepatotoxicity with ECGzNP2 compared to RIF, and uptake of orally administered NP through Peyer's Patches as a feasible strategy for lung targeting is demonstrated.
Abstract: Uptake of nanoparticles through Peyer's Patches following oral administration could enable translocation through lymph to lymphatic organs like the lungs. An important consideration, however, is nanosize and particle hydrophobicity. Furthermore, as delivering the nanoparticles to the intestine where the Peyer's Patches are localized is important, their intact and rapid transit through the stomach into the intestine is highly desirable. We report hydrophobization of mucoadhesive Rifampicin-GantrezAN-119 nanoparticles (GzNP) using a hydrophobic polymer, ethyl cellulose (EC), with the objectives of augmenting Peyer's Patch uptake due to enhanced hydrophobicity and increased intestinal localization as a result of decreased mucoadhesion. RIF-Gantrez-EC nanoparticles (ECGzNP2) exhibited >13% RIF loading and an average particle size of 400-450 nm, which is appropriate for translation through lymph following Peyer's Patch uptake. Higher contact angle (67.3 ± 3.5° vs 30.3 ± 2.1°) and lower mucoadhesion (30.7 ± 4.8 g vs 87.0 ± 3.0 g) of ECGzNP2 over GzNP confirmed hydrophobization and lower mucoadhesion. Fluorescence photomicrographs of intraduodenally administered coumarin-labeled RIF-NP in rats demonstrated higher Peyer's Patch uptake with ECGzNP2, while the increased lung/plasma RIF ratio signified lymph mediated lung targeting. The gastrointestinal transit study in rats, which revealed a significantly higher intestine-to-stomach accumulation ratio with ECGzNP2 (3.4) compared to GzNP (1.0) [ p < 0.05], confirmed availability of the NP in the intestine for Peyer's Patch uptake. Such uptake enabled 182.4 ± 22.6% increase in relative bioavailability, a ∼2-fold higher plasma AUC/MIC ratio and significantly higher lung concentration with ECGzNP2, thereby proposing better efficacy. A significantly higher lung/liver ratio with ECGzNP2 also suggested lower hepatic exposure. The repeated dose 28-day oral toxicity study demonstrated the safety of the nanocarrier and reduced hepatotoxicity with ECGzNP2 compared to RIF. We hereby demonstrate uptake of orally administered NP through Peyer's Patches as a feasible strategy for lung targeting.
19 citations
03 Oct 2018
TL;DR: In this paper, targeted delivery of vitamin D3 employing nanocarriers could enable improved efficacy in a range of therapies, including bone disorders, cancer, psoriasis, infectious diseases, cardiovascular diseases, and degenerative diseases.
Abstract: Nutraceuticals are gaining wide acceptance due to their synergistic nutritional effects and therapeutic value. Vitamin D3 is one such nutraceutical that plays a critical role in health. Vitamin D3 deficiency is a global problem with the major causes attributed to insufficient exposure to sunlight and limited availability of food sources containing vitamin D. The recommended daily intake of vitamin D3 is 400 IU for children and 800 IU for adults. Although available as fortified food supplements and therapeutic formulations, the problems include low bioavailability, rapid metabolism, and low stability. Efforts to overcome these problems are comprised of approaches to confer improved stability and bioavailability. Nanocarriers of vitamin D3 have been effectively employed for improved stability and bioavailability. Vitamin D3, alone or in combination with other drugs, exhibits promise for effective therapy in various conditions, including bone disorders, cancer, psoriasis, infectious diseases, cardiovascular diseases, and degenerative diseases. Furthermore, targeted delivery of vitamin D3 employing nanocarriers could enable improved efficacy in a range of therapies. This multifaceted nutraceutical holds great promise when delivered in nanoformulations for improved management of serious pathologies.