Use of multifunctional systems for the controlled release of therapeutic agents

Date

2023-04-21

Authors

David, Mariya

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Abstract

Despite significant progress in the development of polymeric systems for drug delivery in the last few decades, there is a need for the development of delivery systems that can deliver multiple therapeutic agents simultaneously or in sequence. For this purpose, a multifunctional delivery system, inspired by scaffolds used for tissue engineering applications, was developed. First, a library of methacrylic acid-based nanoparticles was developed using two different synthesis techniques. The hydrophobic to hydrophilic monomer ratio, co-monomer hydrophilicity, and crosslinking density impacted nanoparticle properties, such as swelling behavior and surface charge, as well as loading efficiencies of model therapeutic proteins. The release kinetics of model therapeutic proteins were dependent on nanoparticle hydrophilicity. Protein was released at higher rates from hydrophilic nanoparticles at early time points and hydrophobic nanoparticles at later time points. The synthesized nanoparticles were then conjugated to porous, biodegradable scaffolds. Nanoparticle conjugation and distribution throughout the scaffold was confirmed using scanning electron microscopy. Release of therapeutic proteins was studied from two-phase systems and it was demonstrated that the two-phase system resulted in more sustained protein release with a decreased burst release compared to release from the scaffold alone. Furthermore, it was shown that distinct release profiles were observed based on the composition of nanoparticles attached to the scaffold. The developed systems were then evaluated in vitro for their biocompatibility and ability to promote cell proliferation. All nanoparticles showed minimal cytotoxicity at concentrations up to 1 mg/mL. Furthermore, chitosan scaffolds were shown to promote cell proliferation, with no impact of nanoparticle conjugation on cell growth, indicating that they serve as suitable substrates for cell growth. Finally, the chitosan scaffolds were found to support the differentiation of pre-osteoblast cells, demonstrating their suitability for bone tissue engineering applications. These systems show great promise for drug delivery and tissue engineering applications. The ability to tune the release of therapeutic agents can ultimately provide better treatments for complex diseases and facilitate the formation of functional tissue.

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