Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

Autor: Manna S; Department of Mechanical and Materials Engineering, University of Cincinnati, Cincinnati, OH, United States., Donnell AM; Department of Chemistry, University of Cincinnati, Cincinnati, OH, United States., Kaval N; Department of Chemistry, University of Cincinnati, Cincinnati, OH, United States., Al-Rjoub MF; Department of Mechanical and Materials Engineering, University of Cincinnati, Cincinnati, OH, United States., Augsburger JJ; Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, United States., Banerjee RK; Department of Mechanical and Materials Engineering, University of Cincinnati, Cincinnati, OH, United States. Electronic address: Rupak.banerjee@uc.edu.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2018 Aug 25; Vol. 547 (1-2), pp. 122-132. Date of Electronic Publication: 2018 May 29.
DOI: 10.1016/j.ijpharm.2018.05.066
Abstrakt: Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases.
(Copyright © 2018. Published by Elsevier B.V.)
Databáze: MEDLINE
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