Preparation and Evaluation of Pralidoxime-Loaded PLGA Nanoparticles as Potential Carriers of the Drug across the Blood Brain Barrier

Abstract

Pralidoxime is an organophosphate antidote with poor central nervous system distribution due to a high polarity. In the present study, pralidoxime-loaded poly(lactic-co-glycolic acid) nanoparticles were prepared and evaluated as a potential delivery system of the drug into the central nervous system. The nanoparticles were prepared using double emulsion solvent evaporation method. Poly(lactic-co-glycolic acid) (PLGA) in ethyl acetate made the organic phase and pralidoxime in water made the aqueous phase. The system was stabilized by polyvinyl alcohol. Different drug/polymer ratios were used (1 : 1, 1 : 2, and 1 : 4) and the fabricated particles were characterized for encapsulation efficiency using UV-VIS Spectroscopy; particle size distribution, polydispersity index, and zeta potential using photon correlation spectroscopy; and in vitro drug release profile using UV-VIS Spectroscopy. Mean particle sizes were 386.6 nm, 304.7 nm, and 322.8 nm, encapsulation efficiency was 28.58%, 51.91%, and 68.78%, and zeta potential was 5.04 mV, 3.31 mV, and 5.98 mV for particles with drug/polymer ratios 1 : 1, 1 : 2, and 1 : 4, respectively. In vitro drug release profile changed from biphasic to monobasic as the drug/polymer ratio decreased from 1 : 1 to 1 : 4. Stable pralidoxime-loaded PLGA nanoparticles were produced using double emulsion solvent evaporation techniques.

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

“…Small zeta potential values were obtained for all the studied formulations (,20), which is an indication of encapsulation of the drug in the prepared PLGA NPs. 31 A small value of zeta potential is associated with low particle stability and the tendency of the prepared for aggregation, but separation and lyophilization of the particle with subsequent loading into viscous polymeric solution are expected to retard particle aggregation. Stability of the particles could also be improved by surface modification.…”

Treatment of neurodegenerative disorders through the blood–brain barrier using nanocarriers

“…The results showed that for long-term circulation without any surface modification, the 100 nm nanoparticles worked best because they could escape the liver metabolism (107). This and several other studies suggest that PLGA is a promising candidate for enhancing therapeutic delivery into the CNS (108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120). However, PLGA degrades by bulk erosion, which can lead to premature exposure of the therapeutic to a degradative environment.…”

Comparative in vitro transportation of pentamidine across the blood-brain barrier using polycaprolactone nanoparticles and phosphatidylcholine liposomes

“…The particles were also observed to have higher negative charge of -33.4 ± 8.12 which could induce the repulsive force to the particles when they get into contact with the biological membranes which are negatively charged. However, we suggested that nanoparticles being coated with polysorbate 80 which adsorbs apolipoprotein E would increase the penetration of nanoparticles across the BBB [29,32]. Drug release showed that pentamidine released was slow and constant over 24 h. Drug diffusion and degradation of PCL polymer is usually slow and the release would be expected to start slowly and extend as the polymer erodes [33,34].…”