Encapsulación de puntos de carbono en un hidrogel basado en alginato: Prueba de concepto de liberación controlada de fármacos

Abstract

Drug delivery systems seek to deliver a therapeutic amount of a molecule or compound with a biological or biomedical purpose to the body. These systems are classified into traditional, modified and controlled release. Traditional systems do not feature formulation design that allows targeting the drug to a specific site or controlling the rate of its release. In contrast, controlled release systems have a formulation design that allows them to control the rate of release and/or present a configuration that facilitates the identification of a specific area for its action. Thus, the latter offer advantages over traditional systems such as simplified dosing, reduced adverse effects and increased efficacy of pharmacotherapeutic treatments. Carbon dots (CDs) are nanoparticles that exhibit high solubility in aqueous media, good biocompatibility and non-cytotoxic nature. These particles have been proposed as nanocarriers for drug delivery for controlled release purposes, as they exhibit fluorescent emission in the visible region of the electromagnetic spectrum, increase biodistribution and stability of therapeutic agents to target organs. On the other hand, hydrogels have been used as vehicles in controlled release systems. Hydrogels are polymeric, biocompatible networks that can absorb up to a thousand times their weight in water or water-based fluids, possess viscoelastic properties similar to that of human tissues and allow the encapsulation of different species such as drugs or molecules of biomedical interest. The present work proposes a release system, where carbon dots are encapsulated in an alginate-based hydrogel and a proof of concept of controlled release is performed. This work is linked to the framework project 'Development of the components of a controlled drug release system based on an electroresponsive hydrogel integrated by carbon dots functionalized with curcumin' financed by Fondos Concursables UR-Capital Semilla. This system development process will focus on four stages of development: (i) synthesis of carbon dots by microwave method with citric acid, N,N-dimethylformamide ethanol as starting materials seeking to vary the reaction temperature, characterization of optical properties in order to determine which carbon dots have better properties for use as encapsulated molecule. (ii) The development of the alginate hydrogel and the evaluation of its degradation in response to pH for the design of drug delivery systems. (iii) The encapsulation of carbon dots in the hydrogel and their respective controlled release test. (iv) Additionally, a literature review of protocols for the synthesis of electroresponsive hydrogels is developed. In this project the results of each stage are presented, the synthesized carbon dots evidenced absorption bandwidth in the UV region (200-320 nm) and fluorescence in the blue to cyan region (427-520 nm). Carbon dots at 200°C evidenced higher emission at excitation lengths of 360/380 nm compared to carbon dots at 100°C, 125°C, 150°C and 175°C. In the synthesis of the alginate hydrogel, the ratio of polymer and crosslinker (CaCl2 - NaCl) presented an important role in the degradation rate of the hydrogel in aqueous medium with acidic (pH = 3.2) and basic (pH =8.5) pH characteristics. Moreover, the degradation of hydrogels with alginate and crosslinker ratio (1:1.5) was completed at half time compared to the ratio (1:1). The release profiles of the carbon dots embedded in the hydrogels in acid-base medium did not present trends described in the mathematical models to determine the release kinetics. Therefore, a linearization was performed to obtain a linear behavior. Also, a higher photoluminescence was evidenced in the aqueous medium with basic pH compared to the acidic medium. Literature review, it was found that the techniques to synthesize the conductive polymers used in electroresponsive hydrogels are chemical oxidative, electrochemical or irradiation polymerization. Polyaniline (PAni), polypyrrole (PPy) and PEDOT are the most commonly used conductive polymers due to their biocompatibility and good electrical and electrochemical properties. Oxidative chemical polymerization is the most widely used technique to synthesize these polymers, due to the amount of final production obtained since it presents homogeneous polymerization. However, this technique presents limitations to control the processes and the reagents involved such as oxidant, temperature, solvent.