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Endometriosis is considered a serious public health issue because of the large number of females affected by this illness. Chronic pain management in patients with endometriosis demands new strategies to increase the life quality of these patients. The development of drug delivery systems represents a new approach in pain treatment among endometriosis patients. Diclofenac sodium, one of the most utilized nonsteroidal anti-inflammatory drugs (NSAID), has its own limitations when being used in formulas such as oral, parental, or local applications. In this paper, a series of four drug release formulations based on chitosan, 2-hydroxy-5-nitrobenzaldehyde, and diclofenac sodium salt were prepared in view of the investigation of the drug release ability. The formulations were analyzed from a morphological and supramolecular point of view by scanning electron microscopy and polarized light microscopy. The in vitro drug release ability was investigated by mimicking a physiologic environment. A mathematical model, using the fractal paradigm of motion, is utilized to explain the behaviors of the drug delivery system presented in this paper. These results suggest a great potential of the proposed drug delivery system, based on chitosan and 2-hydroxy-5-nitrobenzaldehyde to improve the diclofenac sodium salt bioavailability, and it may represent a future treatment formula for endometriosis pain., Competing Interests: All authors declare no conflict of interest., (Copyright © 2021 Bogdan Florin Toma et al.)

Two formulations based on diclofenac sodium salt encapsulated into a chitosan hydrogel were designed and prepared, and their drug release was investigated by combining in vitro results with mathematical modeling. To understand how the pattern of drug encapsulation impacted its release, the formulations were supramolecularly and morphologically characterized by scanning electron microscopy and polarized light microscopy, respectively. The mechanism of diclofenac release was assessed by using a mathematical model based on the multifractal theory of motion. Various drug-delivery mechanisms, such as Fickian- and non-Fickian-type diffusion, were shown to be fundamental mechanisms. More precisely, in a case of multifractal one-dimensional drug diffusion in a controlled-release polymer–drug system (i.e., in the form of a plane with a certain thickness), a solution that allowed the model's validation through the obtained experimental data was established. The present research reveals possible new perspectives, for example in the prevention of intrauterine adhesions occurring through endometrial inflammation and other pathologies with an inflammatory mechanism background, such as periodontal diseases, and also therapeutic potential beyond the anti-inflammatory action of diclofenac as an anticancer agent, with a role in cell cycle regulation and apoptosis, using this type of drug-delivery system. [ABSTRACT FROM AUTHOR]

The paper focuses on the development of a multifractal theoretical model for explaining drug release dynamics (drug release laws and drug release mechanisms of cellular and channel-type) through scale transitions in scale space correlated with experimental data. The mathematical model has been developed for a hydrogel system prepared from chitosan and an antimicrobial aldehyde via covalent imine bonds. The reversible nature of the imine linkage points for a progressive release of the antimicrobial aldehyde is controlled by the reaction equilibrium shifting to the reagents, which in turn is triggered by aldehyde consumption in the inhibition of the microbial growth. The development of the mathematical model considers the release dynamic of the aldehyde in the scale space. Because the release behavior is dictated by the intrinsic properties of the polymer–drug complex system, they were explained in scale space, showing that various drug release dynamics laws can be associated with scale transitions. Moreover, the functionality of a Schrödinger-type differential equation in the same scale space reveals drug release mechanisms of channels and cellular types. These mechanisms are conditioned by the intensity of the polymer–drug interactions. It was demonstrated that the proposed mathematical model confirmed a prolonged release of the aldehyde, respecting the trend established by in vitro release experiments. At the same time, the properties of the hydrogel recommend its application in patients with intrauterine adhesions (IUAs) complicated by chronic endometritis as an alternative to the traditional antibiotics or antifungals. [ABSTRACT FROM AUTHOR]