**1. Introduction**

Over the past few decades, polylactide (PLA) has emerged as a common biomaterial in biomedical applications owing to its favorable properties, such as complete biodegradability, mechanical properties, biocompatibility, processability, and transparency [1,2]. A PLA possesses two types of three-dimensional helical structures that twist in clockwise (D-configured) and counter-clockwise (L-configured) directions. Since Ikada et al. first reported stereocomplex formation between enantiomeric PLA in 1987 [3], stereocomplexation between poly(D-lactide) (PDLA) and poly(L-lactide) (PLLA) enantiomers has been the subject of continuous study. This research has accelerated with the rapid growth of practical use and the potential worth of PLA as a representative biodegradable polymer. Stereocomplex crystallites with a 3/1 helical structure in the PLA material can overcome inferior mechanical and thermal characteristics of homo-crystallites having a 10/3 helical

**Citation:** Im, S.H.; Im, D.H.; Park, S.J.; Chung, J.J.; Jung, Y.; Kim, S.H. Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review. *Molecules* **2021**, *26*, 2846. https://doi.org/ 10.3390/molecules26102846

Academic Editors: Marek Brzezi ´nski and Malgorzata Ba´sko

Received: 8 April 2021 Accepted: 10 May 2021 Published: 11 May 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

structure. The combination of two enantiomeric polymers increases the melting point (*Tm*) and crystallinity through the compact orientation of crystals in the material. Ultimately, this change in a biodegradable polymer can result in an increase in thermal stability, mechanical strength, resistance against solvent penetration, and external forces. Stereocomplex crystals in PLA have commonly been formed by solution blending, melt blending, emulsion blending, precipitation into non-solvent, and supercritical fluid (SCF) techniques [4–9]. Each method has different advantages and disadvantages regarding the yield and stereocomplexation efficiency, processability, solubility, time, and cost.

Recently, numerous studies have reported that stereocomplex polylactide (sc-PLA) with improved physical characteristics can be used in drug delivery and as molecular carriers [10–12]. Nanoparticles, such as microspheres and micelles of sc-PLA, have the advantage of controlling drug uptake and release patterns through their synthesis and modification, as well as natural adsorption. Despite these advantages, many challenges remain for the application of sc-PLA as a drug carrier, including inferior encapsulation efficiency, low stability of hydrophilic drugs and proteins, and the burst release phenomenon. To resolve these issues, various strategies, such as polymerization, self-assembly, surface modification, and polymer grafting, have been studied [13–17]. This review discusses various synthesis and processing methods for the application of sc-PLA as a drug and molecular carrier, and it suggests future directions to stimulate the application of sc-PLA with therapeutic molecules in drug delivery systems and biomedical applications.
