5-Fluorouracil Release from Chitosan-Based Matrix.Experimental and Theoretical Aspects

Roxana Iancu,Viorel-Puiu Paun,Sorin Stratulat,Maria-Alexandra Paun,Vladimir-Alexandru Paun,Mihail Frasila,Maricel Agop,Stefan Andrei Irimiciuc

doi:10.37358/mp.20.3.5392

Abstract

A series of four drug release formulations based on 5-fluorouracil encapsulated into a chitosan-based matrix were prepared by in situ hydrogelation with 3,7-dimethyl-2,6-octadienal. The formulations were investigated from structural and morphological aspects by FTIR spectroscopy, polarized light microscopy and scanning electron microscopy. It was established that 5-fluorouracil was anchored into the matrix as crystals, whose dimension varied as a function of the crosslinking density. The in vitro drug release simulated into a media mimicking the physiological environment revealed a progressive release of the 5-fluorouracil, in close interdependence with the crosslinking density. In the context of Pharmacokinetics behavioral analysis, a new mathematical procedure for describing drug release dynamics in polymer-drug complex system is proposed. Assuming that the dynamics of polymer-drug system�s structural units take place on continuous and nondifferentiable curves (multifractal curves), we show that in a one-dimensional hydrodynamic formalism of multifractal variables the drug release mechanism (Fickian diffusion, non-Fickian diffusion, etc) are given through synchronous dynamics at a differentiable and non-differentiable scale resolutions. Finally, the model is confirmed by the empirical data.

Highlights

Chitosan based formulations are of increasing interest in the drug delivery field, due to its intrinsic properties such as biocompatibility and biodegradability, which recommend it for in vivo applications [1,2,3]
The presence of the 5-fluorouracil into formulations was evidenced by polarized light microscopy (Figure 1), which revealed the clear segregation of the drug into the hydrogels with high crosslinking density (U1, U2), while for the hydrogel formulations with lower crosslinking density (U4) a birefringent, granular texture was observed, characteristic for submicrometric dimensions of the crystals, which fall under the detection limit of the equipment [22,23]
A series of drug delivery systems were prepared by encapsulation of the 5-fluorouracil into a hydrogel formed by crosslinking chitosan with 3,7-dimethyl-2,6-octadienal

Summary

Introduction

Chitosan based formulations are of increasing interest in the drug delivery field, due to its intrinsic properties such as biocompatibility and biodegradability, which recommend it for in vivo applications [1,2,3]. In order to further improve the chitosan ability to anchor large amounts of drugs and to release them in a controlled manner, many attempts were pursued consisting mainly in chitosan crosslinking with various agents. In this line of thoughts, an eco-friendly method was developed by crosslinking chitosan with eco-friendly monoaldehydes [4,5,6,7,8,9,10]. By using the natural aldehyde: 3,7-dimethyl-2,6-octadienal, known under the commercial name: citral, hydrogels, with excellent biocompatibility and biodegradability which were further developed as matrix for drug delivery systems, were obtained. The homogeneity assumption in its various forms (homogenous kinetic space, law of mass etc.) has become almost dogmatic in Pharmacokinetics (PK).The functionality of such a hypothesis allowed the development of a class of differentiable models in the description of dynamics

Methods

Results

Conclusion