Preparation and modeling of three\u2010layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release

Miljan Milosevic,Vladimir Simic,Petar S Uskokovic,Mirjana Grkovic,Milos Bjelovic,Dusica B Stojanovic,Milos Kojic

doi:10.1038/s41598-020-68117-9

Abstract

The authors present the preparation procedure and a computational model of a three‐layered fibrous scaffold for prolonged drug release. The scaffold, produced by emulsion/sequential electrospinning, consists of a poly(d,l-lactic-co-glycolic acid) (PLGA) fiber layer sandwiched between two poly(ε-caprolactone) (PCL) layers. Experimental results of drug release rates from the scaffold are compared with the results of the recently introduced computational finite element (FE) models for diffusive drug release from nanofibers to the three-dimensional (3D) surrounding medium. Two different FE models are used: (1) a 3D discretized continuum and fibers represented by a simple radial one-dimensional (1D) finite elements, and (2) a 3D continuum discretized by composite smeared finite elements (CSFEs) containing the fiber smeared and surrounding domains. Both models include the effects of polymer degradation and hydrophobicity (as partitioning) of the drug at the fiber/surrounding interface. The CSFE model includes a volumetric fraction of fibers and diameter distribution, and is additionally enhanced by using correction function to improve the accuracy of the model. The computational results are validated on Rhodamine B (fluorescent drug l) and other hydrophilic drugs. Agreement with experimental results proves that numerical models can serve as efficient tools for drug release to the surrounding porous medium or biological tissue. It is demonstrated that the introduced three-layered scaffold delays the drug release process and can be used for the time-controlled release of drugs in postoperative therapy.

Highlights

The authors present the preparation procedure and a computational model of a three‐layered fibrous scaffold for prolonged drug release
In the sequential electrospinning process, the three-layer scaffold was designed as follows: first, the PCL fibrous layer was electrospun for 90 min, the second layer of PLGA fibers containing Rhodamine B (RhB) was electrospun for 60 min and cut at dimensions 2.5 × 3 cm
In order to represent radial diffusion within the fiber and volume belonging to the common point, we introduced radial 1D element as fictitious element in the finite element (FE) mesh representation

Summary

Introduction

The authors present the preparation procedure and a computational model of a three‐layered fibrous scaffold for prolonged drug release. Fibers are preferably prepared using a biodegradable p olymer[7], and their main function is targeted and cites specific drug delivery in human b ody[1,2,3,4,5], without any burst r elease[7], and with improved physicochemical properties[6]. It is known that both degradation and erosion change the properties of the polymer matrix: porosity and PLGA M W14 Those factors dramatically change the drug release nature and have to be taken into account in drug transport models[14]. Another commonly used synthetic biodegradable polymer, poly(є-caprolactone (PCL), belongs to the group of promising b iomaterials[9] due to its biodegradability nature and b iocompatibility[7]. Various s tudies[24,25,26] showed that PCL fibers are potential drug delivery o ptions[7], for any kind and type of drug

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