PLGA Core-Shell Nano/Microparticle Delivery System for Biomedical Application

Core–shell particles are very well known for their unique features. Their distinctive inner core and outer shell structure allowed promising biomedical applications at both nanometer and micrometer scales. The primary role of core–shell particles is to deliver the loaded drugs as they are capable of sequence-controlled release and provide protection of drugs.

Among other biomedical polymers, poly (lactic-co-glycolic acid) (PLGA), a food and drug administration (FDA)-approved polymer, has been recognized for the vehicle material. This review introduces PLGA core–shell nano/microparticles and summarizes various drug-delivery systems based on these particles for cancer therapy and tissue regeneration. Tissue regeneration mainly includes bone, cartilage, and periodontal regeneration.

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Introduction

A drug-delivery system (DDS) based on nano/microparticles has gained attention during the last few decades since these nano/micro vehicles protect loaded drugs, serve as a localized scaffold, and control its release kinetics. These features allow us to have the same treatment effect with less drug dosage, thus reducing possible side effects [1]. What makes nano/microparticle-based DDS even more attractive is the fact that these particles can be modified to have various abilities, like targeting, multiple drug delivery, or being responsive to light, pH, temperature, magnetic field, or different extracellular environments [2,3].

Drug carriers should be compatible with living tissue and degrade into non-toxic organic compounds. A widely used drug carrier is poly(lactic-co-glycolic acid) (PLGA), which is also approved by the U.S. Food and Drug Administration (FDA), thanks to its excellent biodegradable and biocompatible properties [4]. Along with PLGA, poly(lactic acid) (PLA), poly(vinyl alcohol) (PVA), poly(L-lactic acid) (PLLA), poly(ethylene glycol) (PEG), poly(glycolic acid) (PGA), and chitosan (CS) have also been frequently used since they have good biodegradability [5]. The common problem of utilizing PLGA arises when encapsulating hydrophilic agents, since PLGA is a highly hydrophobic polymer. Also, to prepare PLGA, toxic organic solvents are usually used, and these solvents remain in the particle [6].
Core–shell microspheres have two or more distinct layers made of the same or different materials which can each be loaded with bioactive molecules [7]. Depending on the purpose, these core–shell particles have varying core shapes, internal structures, shell thicknesses, and surface morphologies. These factors are the key determinants of loading efficiency and release kinetics [8]. The size of the microspheres usually ranges between 10–200 μm because too small microspheres (< 10 μm) will get engulfed by immune cells and too big microspheres (> 200 μm) will cause inflammation [8]. Numerous techniques for synthesizing core–shell microspheres are developed, including polymerization, spray drying, solvent evaporation, and self-assembly [9]. Using microfluidic devices allows fabricating microspheres with uniform size and thickness, and also has the advantages of higher encapsulation efficiency for both hydrophilic and hydrophobic agents [10].

Cancer therapy using PLGA microspheres includes chemotherapy, photothermal therapy, hormonal therapy, immunotherapy, and others. Like other applications, two or more cancer treatment methods are frequently combined to seek synergistic effects [11,12,13,14,15]. Microspheres are often targeted to cancer cells by adding receptors to the outermost layer or by making them respond to cancer-specific extracellular environments [12]. Core–shell microparticles are also applied to tissue regeneration, as an alternative solution for transplanting and autologous cell therapy. Some application examples include bone regeneration, cartilage, and periodontal regeneration. Microspheres up to 100 μm are said to be suitable for these cases [16]. Strategy that sequentially releases growth factor and differentiation factor is commonly used [8,17,18,19,20,21]. As per our knowledge, several review literatures have been published related to PLGA microspheres for biomedical applications [22,23,24,25]. However, a smaller number of reviews have been reported on the PLGA core–shell microsphere [26,27]. In this review, we summarized the current state of core–shell nano/micro PLGA particles for drug delivery, cancer therapy, and tissue regeneration. In the tissue regeneration section, we especially include bone, cartilage, and periodontal regeneration.

Article information: Kim, S.M.; Patel, M.; Patel, R. PLGA Core-Shell Nano/Microparticle Delivery System for Biomedical Application. Polymers 2021, 13, 3471. https://doi.org/10.3390/polym13203471