title: Surface modified PLGA nanoparticles for brain targeting of Bacoside-A.
abstract: The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70-200 nm) with relatively low polydispersity index (0.391 ± 1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11 ± 7.11%, with a drug loading capacity of 20.5 ± 1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04 ± 2.55% in 48 h. When compared to pure drug solution (2.56 ± 1.23 μg/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94 ± 1.74 μg/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain.
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India. Electronic address: sajanjose@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Jose
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Sowmya
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India; Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: T A
authors.initials: TA
authors.lastname: Cinu
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India.
authors.forename: N A
authors.initials: NA
authors.lastname: Aleykutty
authors.affiliation: Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, India.
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Research Centre in Biomedicine (CEBIMED), Fernando Pessoa University, Praça 9 de Abril, 349, P-4249-004 Porto, Portugal; Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, P-4200-150 Porto, Portugal; Institute of Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, 5001-801 Vila-Real, Portugal. Electronic address: eliana@ufp.edu.pt.
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D012503:Saponins; D013501:Surface-Active Agents; D014315:Triterpenes; C500175:bacoside A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Bacoside-A; Blood brain barrier; Nanoparticles; Poly(lactic-co-glycolic acid)