Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies.
Sustained release nanoparticulate formulations of Rivastigmine tartrate (RT) were prepared, optimized (using factorial design) and characterized using the biodegradable polymers, PLGA and PBCA as carriers. The pharmacodynamic performances of the nanoparticles (NPs) were evaluated for brain targeting and memory improvement in scopolamine-induced amnesic mice using Morris Water Maze Test. PLGA NPs were prepared by nanoprecipitation technique, while PBCA NPs were prepared by emulsion polymerization technique. Effect of key formulation variables on particle size (PS) and percentage drug entrapment (PDE) of NPs was studied by using factorial design. PLGA NPs showed PS of 135.6±4.2nm and PDE of 74.46±0.76 %, whereas PBCA NPS showed PS of 146.8±2.6nm and PDE of 57.32±0.91%. FTIR and GPC characterization confirmed complete polymerization of n-butyl cyanoacrylate (nBCA) monomer into PBCA. DSC thermograms indicated that RT was dispersed as amorphous state in both PLGA and PBCA NPs. TEM studies indicated that the NPs were spherical. In vitro studies showed 30.86±2.07% and 43.59±3.80% release from PLGA and PBCA NPs in 72h, respectively. Pharmacodynamic study demonstrated faster regain of memory loss in amnesic mice with both PLGA and PBCA NPs when compared to RT solution. This indicates rapid and higher extent of transport of RT into the mice brain and thus shows the suitability of both NPs as potential carriers for providing sustained brain delivery of RT.
Joshi
Shrinidh A
SA
TIFAC Centre of Relevance and Excellence, Centre of PG studies and Research, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donors Plaza, Fatehgunj, Vadodara 390002, Gujarat, India.
Chavhan
Sandip S
SS
Sawant
Krutika K
KK
D000647:Amnesia / Q000188:drug therapy*; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000068836:Rivastigmine; D012601:Scopolamine
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012601:Scopolamine; D004659:Enbucrilate; D000068836:Rivastigmine