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Clustered randomly interspaced short palindromic repeats (CRISPRs) and its associated endonuclease protein, i.e., Cas9, have been discovered as an immune system in bacteria and archaea; nevertheless, they are now being adopted as mainstream biotechnological/molecular scissors that can modulate ample genetic and nongenetic diseases via insertion/deletion, epigenome editing, messenger RNA editing, CRISPR interference, etc. Many Food and Drug Administration-approved and ongoing clinical trials on CRISPR adopt ex vivo strategies, wherein the gene editing is performed ex vivo, followed by reimplantation to the patients. However, the in vivo delivery of the CRISPR components is still under preclinical surveillance. This review has summarized the nonviral nanodelivery strategies for gene editing using CRISPR/Cas9 and its recent advancements, strategic points of view, challenges, and future aspects for tissue-specific in vivo delivery of CRISPR/Cas9 components using nanomaterials.

Purpose: Intravitreal administration of drug molecules is one of the most common routes for treating posterior segment eye diseases. However, the properties of vitreous humour changes with the time. A number of ocular complications such as liquefaction of the vitreous humour, solidification of the vitreous humour in the central vitreous cavity and detachment of the limiting membrane due to the shrinking of vitreous humour are some of the factors that can drastically affect the efficacy of therapeutics delivered via intravitreal route. Although significant research has been conducted for studying the properties of vitreous humour and its changes during the ageing process, there have been limited work to understand the effect of these changes on therapeutic efficacy of intravitreal drug delivery systems. Therefore, in this review we discussed both the coomposition and characteristics of the vitreous humour, and their subsequent influence on intravitreal drug delivery. Methods: Articles were searched on Scopus, PubMed and Web of Science up to March 2022. Results: In this review, we discussed the biological composition and biomechanical properties of vitreous humour, methods to study the properties of vitreous humour and the changes in these properties and their relevance in ocular drug delivery field, with the aim to provide a useful insight into these aspects which can aid the process of development of novel intravitreal drug delivery systems. Conclusions: The composition and characteristics of the vitreous humour, and how these change during natural aging processes, directly influence intravitreal drug delivery. This review therefore highlights the importance of understanding the properties of the vitreous and identifies the need to achieve greater understanding of how changing properties of the vitreous affect the therapeutic efficacy of drugs administered for the treatment of posterior eye diseases. [ABSTRACT FROM AUTHOR]

Purpose: Age-related macular degeneration is a vision-threatening disorder affecting the posterior segment of the eye. Drug delivery to the posterior segment is challenging owing to the complex anatomical and physiological structure, necessitating monthly injections of antivascular endothelial growth factors. Thermoresponsive hydrogels provide sustained drug delivery and ease of injection, due to their sol-gel transition. Poly (N-isopropyl acrylamide) (PNIPAAm) is a widely researched thermoresponsive hydrogel; however, insufficient wet strength and a wide mesh network make it inept for the entrapment of small molecules. Methods: A novel approach of grafting PNIPAAm with chitosan is exploited. A chitosan concentration altered in 10%, 30%, and 50% compared to PNIPAAm is investigated for entrapment of a small-molecular weight, hydrophilic drug, sunitinib (SUN), a multiple tyrosine kinase receptor inhibitor. Furthermore, these hydrogels were characterized using 1H-NMR, FTIR, differential scanning calorimetry (DSC), and thermogravimetric analysis for chemical characterization and viscosity, swellability, syringeability, degradation, and In-vitro permeation using Franz-diffusion cell. Results:In-vitro drug release kinetics suggested that the release of SUN could be controlled with the percentage of chitosan grafting; however, gel strength (3%-5% w/v) of 30% Cs-g-PNIPAAm did not significantly affect percentage drug release. Sustained release of SUN was observed for 1 month. In-vitro permeation studies on porcine sclera suggested that a thermoresponsive gel of chitosan grafted PNIPAAm (Cs-g-PNIPAAm) was able to sustain the drug release by 40%, compared to SUN solution. Conclusions: The study indicates that the synthesized Cs-g-NIPAAm hydrogel has the potential to serve as a tailorable injectable platform for intrascleral drug delivery applications. [ABSTRACT FROM AUTHOR]

Infections caused by fungal species via their existence as biofilms on medical devices can cause organ damage via candidiasis and candidemia. Different Candida species like Candida albicans can pose a serious threat by resisting host's immune system and by developing drug resistance against existing antimycotic agents. Therefore, targeting of fungal membranes can be used as an alternative strategy to combat the fungal infections. Here, we present screening of different amphiphiles based on cholic acid against different Candida strains as these amphiphiles can act as potent membrane-targeting antimycotic agents. Structure-activity correlations, biochemical assays and electron microscopy studies showed that amphiphiles having 4 and 6 carbon chains are most potent, safe and can act on the fungal membranes. Candida albicans did not show emergence of drug resistance on repeated usage of these amphiphiles unlike fluconazole. We show that these amphiphiles can prevent the formation of biofilms and also have the ability to degrade preformed biofilms on different substrates including acrylic teeth. We further demonstrate that amphiphiles 4 and 6 can clear the Candida albicans wound infections and prevent the biofilm formation on indwelling devices in murine models. Therefore, amphiphiles derived from cholic acid and their coatings provide suitable alternatives for inhibiting the fungal infections.