Development of a Long-Term Drug Delivery System with Levonorgestrel-Loaded Chitosan Microspheres Embedded in Poly(vinyl alcohol) Hydrogel

Abstract

This study reports on the fabrication of a controlled release system for the delivery of levonorgestrel (LNG) for long-term contraception. LNG was encapsulated in chemically cross-linked chitosan (CS) microspheres, and microspheres presented a spherical geometry with a good particle size distribution (polydispersity index (PDI) < 0.1). The LNG-CS microspheres were classified based on their particle size range, <63, 63−125, and 125−300 μm, where the 125−300 μm particles were selected to be incorporated into a physically cross-linked and annealed PVA hydrogel matrix to prolong the drug release. PVA concentrations and the annealing treatment influenced the swelling behavior of PVA hydrogels. Fourier transform infrared (FTIR) spectroscopy indicated that CS was successfully crosslinked through the formation of a Schiff base; the PVA hydrogel was formed through hydrogen bonding without reacting with LNG, which was only physically entrapped, thus maintaining its stability. Differential scanning calorimetry (DSC) showed that freeze−thaw and annealing processes increased the degree of crystallinity in the PVA hydrogel. In vitro drug release assessments for all formulations showed zero order without any burst release. Over a period of 100 days, 34, 27, and 21% of LNG was released from the CS-LNG microspheres in the size ranges < 63, 63−125, and 125−300 μm, respectively, while only 14, 11, and 9% of LNG was released when the CS-LNG microspheres were incorporated into 10, 15, and 20% PVA hydrogels, respectively. The drug release kinetics exhibited both diffusion-and swelling-controlled mechanisms following the Korsmeyer−Peppas model. This work presents a promising delivery system for long-term contraception with controlled zero-order release behaviors.

A freeze–thaw PVA hydrogel loaded with guava leaf extract: physical and antibacterial properties

“…The freezing stage results in the formation of hexagonal networks of hydrogen bonds with the water molecules present in the hydrogel network. 55 The one-way ANOVA test showed that there was a signicant difference between groups (p < 0.05) in the hydrogel density. The PGL0 and PGL1 hydrogels signicantly had the highest density compared to other groups.…”

Recent progress in advanced biomaterials for long-acting reversible contraception

“…Long et al . proposed a controlled releasing system in which LNG was chemically cross-linked and encapsulated in CS to form CS-LNG microspheres [ 9 ]. The microspheres had a concentrated particle size distribution and significantly prolonged the drug release.…”

“…F Equilibrium swelling ratio of PVA hydrogels. G Cumulative LNG release from PVA hydrogel in vitro (Reprinted with permission from reference [ 9 ]. Copyright 2019 American Chemical Society) …”

Crosslinking Trends in Multicomponent Hydrogels for Biomedical Applications

“…Lately, synthetic polymer was combined with natural polymers to enhance the biological and mechanical properties of resulting hydrogels, such as chitosan/PEG, agarose-PAM, agarose/polydopamine hydrogel, chitosan/PAM hydrogel, and chitosan-PVA. [43][44][45][46][47][48] In recent years, the medical field has attracted projects towards the formulations of innovative hybrid-hydrogels with a synergistic combination of natural and biocompatible synthetic polymers, with the aim to protect the environment from harmful chemicals and reduce production-costs, which indirectly affect human life. Since hydrogels are used in a range of biomedical applications, such as: tissue engineering, [49] wound healing, [50,51] drug carriers, [52] cancer treatments, [53,54] etc., the gels produced, usually come directly into contact with tissues, blood vessels, internal organs, and as such, can affect the human body in many ways.…”