Design of Estradiol Loaded PLGA Nanoparticulate Formulations: A Potential Oral Delivery System for Hormone Therapy

Abstract

Estradiol (E2), a highly lipophilic molecule with good oral absorption but poor oral bioavailability, was incorporated into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve its oral bioavailability. Nanoparticles were prepared by using polyvinyl alcohol (PVA) or didodecyldimethylammonium bromide (DMAB) as stabilizer, leading to negatively (size 410.9+/-39.4 nm) and positively (size 148.3+/-10.7 nm) charged particles, respectively. Both preparations showed near zero order release in vitro with about 95% drug being released within 45 and 31 days for PVA and DMAB, respectively. In situ intestinal uptake studies in male Sprague-Dawley (SD) rats showed higher uptake of DMAB stabilized nanoparticles. Following oral administration to male SD rats, E2 could be detected in blood for 7 and 2 days from DMAB and PVA stabilized nanoparticles, respectively. Histopathological examination and blood counts indicated the absence of inflammatory response. These data suggest that DMAB stabilized PLGA nanoparticles have great potential as carriers for oral delivery of estradiol.

Pharmacokinetics and tissue distribution studies of orally administered nanoparticles encapsulated ethionamide used as potential drug delivery system in management of multi-drug resistant tuberculosis

“…The increase in AUC 0-∞ of ethionamide in the case of drug-loaded nanoparticles may also be explained by the prolonged release of ethionamide from nanoparticles in the blood as well as decreased clearance of drug from the circulation. Similar results have been reported in mice and guinea pigs following administration of other drug-loaded PLGA nanoparticles (Radwan et al, 1999;Pandey et al, 2003a;Hariharan et al, 2006;Drummond et al, 2009;Kalaria et al, 2009;Veera Reddy et al, 2009).…”

“…This is also because of slow release of ethionamide from nanoparticles due to the higher biodegradation time of the drug-loaded nanoparticles (Hariharan et al, 2006). Moreover, the proportionate increase in the AUC values with doubling the dose (equivalent to 130 mg/kg to 260 mg/kg of ethionamide) of nanoparticles suggest that dose adjustment of nanoparticulate formulation is possible.…”

Formulation of Catechin Hydrate Nanocapsule and Study of its Bioavailability

“…A modified emulsiondiffusion-evaporation method [9] was used to make nanocapsules of catechin hydrate and sodium metaborate. CH (5 mg) was dissolved in 1 mL ethyl acetate and 5 mg SMB in 1 mL water.…”

“…However identical cellular uptake was noticed for both the cases. This method has been used to encapsulate a wide variety of hydrophobic drugs including coenzyme Q [14], ellagic acid [15], estradiol [9], taxol [16,17], ellagic acid [15] and camptothecin [18].…”

From polymeric particles to multifunctional nanocapsules for biomedical applications using the miniemulsion process

“…In principle, peptides and proteins were successfully encapsulated in a microencapsulation process by using the doubleemulsion technique, [39][40][41] the emulsification/solvent evaporation, the diffusion method, [42][43][44] the salting-out procedure, 45 or the layer-by-layer (LbL) technique. The LbL technique starts with a template as core onto which alternately positively and negatively charged polyelectrolyte layers can be added.…”