Chitosan: A Good Candidate for Sustained Release Ocular Drug Delivery Systems

This chapter focuses on the eye, one of the most important organs of humans. Current data on pathophysiology of the human eye are presented in direct correlation with a range of therapeutic products, with a well-known and widely used material, namely chitosan. Applications of chitosan biopolymer are described in the development of innovative, modern, therapeutic devices and solutions. Thus, chitosan is a good excipient either for classic drop-type ocular systems, as well as for complex drug systems such as nanostructures (nanoparticles, nanomicelles and nanosuspensions), liposomes, microemulsions, microspheres, in situ hydrogels and inserts or implants. A number of disadvantages for ocular administration of the drugs are thus overcome

Mitochondrial respiratory complex I probed by delayed luminescence spectroscopy.

The role of mitochondrial complex I in ultraweak photon-induced delayed photon emission (delayed luminescence (DL)) of human leukemia Jurkat T cells was probed by using complex I targeting agents like rotenone, menadione, and quercetin. Rotenone, a complex I-specific inhibitor, dose-dependently increased the mitochondrial level of reduced nicotinamide adenine dinucleotide (NADH), decreased clonogenic survival, and induced apoptosis. A strong correlation was found between the mitochondrial levels of NADH and oxidized flavin mononucleotide (FMNox) in rotenone-, menadione- and quercetin-treated cells. Rotenone enhanced DL dose-dependently, whereas quercetin and menadione inhibited DL as well as NADH or FMNox. Collectively, the data suggest that DL of Jurkat cells originates mainly from mitochondrial complex I, which functions predomi- nantly as a dimer and less frequently as a tetramer. In individual monomers, both pairs of pyridine nucleotide (NADH/reduced nicotinamide adenine dinucleotide phosphate) sites and flavin (FMN-a/FMN-b) sites appear to bind cooperatively their specific ligands. Enhancement of delayed red-light emission by rotenone suggests that the mean time for one-electron reduction of ubiquinone or FMN-a by the terminal Fe/S center (N2) is 20 or 284 μs, respectively. All these findings suggest that DL spectroscopy could be used as a reliable, sensitive, and robust technique to probe electron flow within complex I in situ. © 2013 Society of Photo-Optical Instrumentatio

Chitosan-Based In Situ Gels for Ocular Delivery of Therapeutics: A State-of-the-Art Review

Ocular in situ gels are a promising alternative to overcome drawbacks of conventional eye drops because they associate the advantages of solutions such as accuracy and reproducibility of dosing, or ease of administration with prolonged contact time of ointments. Chitosan is a natural polymer suitable for use in ophthalmic formulations due to its biocompatibility, biodegradability, mucoadhesive character, antibacterial and antifungal properties, permeation enhancement and corneal wound healing effects. The combination of chitosan, pH-sensitive polymer, with other stimuli-responsive polymers leads to increased mechanical strength of formulations and an improved therapeutic effect due to prolonged ocular contact time. This review describes in situ gelling systems resulting from the association of chitosan with various stimuli-responsive polymers with emphasis on the mechanism of gel formation and application in ophthalmology. It also comprises the main techniques for evaluation of chitosan in situ gels, along with requirements of safety and ocular tolerability

Paradigm Shift for Endometriosis and the Potential Role of Genetic Testing – Going Beyond the 2022 ESHRE Guidelines for Endometriosis

Endometriosis is a chronic inflammatory gynecological disease affecting 190 million women or 10% of women of reproductive age worldwide. The disease is marked by the presence of endometrial-like tissue outside the uterus, being associated in many cases with chronic pain and infertility. The current recommendations of international professional societies underline the need for laparoscopy, eventually followed by histological verification, as the gold standard for diagnosis. However, many societies recommend the initiation of specific treatment before obtaining a definitive surgical diagnosis. Various national and international societies have released guidelines for endometriosis assessment based on biomarkers; however, none of these recommendations proved to be clinically useful or able to replace diagnostic laparoscopy. In recent years it was demonstrated that oxidative stress, defined as an imbalance between reactive oxygen species and antioxidants that is directly linked with an increased inflammatory response in the peritoneal cavity, may be involved in the pathophysiology of endometriosis. The identification of a genetic predisposition for endometriosis can identify the patients at risk and may help clinicians promptly initiate therapeutic management of their patients in order to ameliorate their prognosis

Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems

The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action

Chitosan-Based In Situ Gels for Ocular Delivery of Therapeutics: A State-of-the-Art Review

Ocular in situ gels are a promising alternative to overcome drawbacks of conventional eye drops because they associate the advantages of solutions such as accuracy and reproducibility of dosing, or ease of administration with prolonged contact time of ointments. Chitosan is a natural polymer suitable for use in ophthalmic formulations due to its biocompatibility, biodegradability, mucoadhesive character, antibacterial and antifungal properties, permeation enhancement and corneal wound healing effects. The combination of chitosan, pH-sensitive polymer, with other stimuli-responsive polymers leads to increased mechanical strength of formulations and an improved therapeutic effect due to prolonged ocular contact time. This review describes in situ gelling systems resulting from the association of chitosan with various stimuli-responsive polymers with emphasis on the mechanism of gel formation and application in ophthalmology. It also comprises the main techniques for evaluation of chitosan in situ gels, along with requirements of safety and ocular tolerability