Development of 3D-Printed Layered PLGA Films for Drug Delivery and Evaluation of Drug Release Behaviors
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Research Article Development of 3D-Printed Layered PLGA Films for Drug Delivery and Evaluation of Drug Release Behaviors Ioannis Serris,1 Panagiotis Serris,1 Kathleen M. Frey,1 and Hyunah Cho1,2
Received 12 June 2020; accepted 17 August 2020 Abstract. 3D printing has been widely used to rapidly manufacture a variety of solid dosage forms on-demand, without sacrificing precision. This study used extrusion-based 3D printing to prepare single-layered, tri-layered, and core-in-shell poly(lactic-co-glycolic acid) (PLGA) films carrying paclitaxel and rapamycin in combination or lidocaine alone. Each layer was composed of either low molecular weight (MW) PLGA or high MW PLGA. In vitro drug release kinetics of paclitaxel, rapamycin, and lidocaine for PLGA films were assessed and compared with PLGA–polyethylene glycol (PEG)–PLGA hydrogel discs. Regardless of the structure of PLGA film, paclitaxel (half-time: 54–63 days) was released faster than when compared with rapamycin (half-time: 74–80 days). In contrast, singlelayered PLGA–PEG–PLGA discs released rapamycin (half-time 5.7 h) at a more rapid rate than paclitaxel (half-time: 7.3 h). Single-layered PLGA–PEG–PLGA discs enabled a faster drug release than PLGA films, noting that the disc matrices dissolve in water in 24 h. Similarly, lidocaine incorporated in PLGA films (half-time: 13–36 days) exhibited slower release patterns than that in PLGA–PEG–PLGA discs (half-time: 2.6 h). In vitro drug release patterns were explained using molecular models that simulate drug-polymer interactions. Analysis of models suggested that drug–polymer interactions, location of each drug in the polymeric matrix, and solubility of drugs in water were major factors that determine drug release behaviors from the polymeric films and discs. KEY WORDS: 3D printing; PLGA; dilm; drug delivery; drug release.
INTRODUCTION Three-dimensional (3D) printing is the process of using computer-aided design (CAD) to produce 3D objects (1). This manufacturing process can be either subtractive or additive (2). With subtractive manufacturing, a larger mass of material is drilled, cut, carved, or milled to create the desired object. Through additive manufacturing, an object is built by depositing layers of printable materials. The additive manufacturing process, also known as 3D printing (2), is vastly used due to the ability to rapidly build intricate designs without material wastage. With the versatility and ease of 3D Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-020-01790-1) contains supplementary material, which is available to authorized users. 1
Pharmaceutical Sciences, School of Pharmacy and Health Sciences, Fairleigh Dickinson University, 230 Park Avenue, Florham Park, New Jersey 07932, USA. 2 To whom correspondence should be addressed. (e–mail: [email protected])
printing, various dosage forms can be designed and structured for specific needs. Personalized medicine, which customizes medications to specific patients’ needs (3), has been proposed as a method to
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