A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

Abstract

Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.

State-of-the-Art Advances and Current Applications of Gel-Based Membranes

“…Unlike rigid ceramic membranes or certain polymeric membranes, gel-based membranes are inherently soft and flexible, which can reduce the risk of fracturing under mechanical stress [43,44]. Despite their soft nature, many gel-based membranes exhibit remarkable stability under various thermal and chemical conditions, especially when designed with specific cross-linkers or additives [45,46]. Also, the high water content and hydrophilic nature of gel-based membranes can reduce the affinity of foulants to the membrane surface, leading to decreased fouling tendencies in applications like water purification [47,48].…”

Polymeric Gel Systems Cytotoxicity and Drug Release as Key Features for their Effective Application in Various Fields of Addressed Pharmaceuticals Delivery

“…Unlike physically cross-linked gels, chemically cross-linked gels can be toxic to the human body due to the entry into the bloodstream of toxic, carcinogenic and teratogenic residual cross-linking agents, such as glutaraldehyde, and the occurrence of immunological reactions on them. Therefore, to use chemically cross-linked gels in pharmacology, it is necessary to purify ready-made gels from low-molecular-weight cross-linking agents using dialysis or use pre-synthesized non-toxic and biodegradable polysaccharide cross-linking agents [ 97 ], biodegradable cystamine containing disulfide bonds [ 109 ], and genipin for cross-linking of collagen, gelatin, chitosan and its derivatives [ 110 ], tetraethyl orthosilicate and graphene oxide for crosslinking of sodium alginate [ 111 ], tetraethyl orthosilicate for crosslinking of chitosan and guar gum with hydroxyl groups [ 112 ], vanillin and citric acid for crosslinking chitosan [ 113 ] and others. The use of more reactive cross-linking agents makes it possible to achieve a greater degree of cross-linking of the polymers, which leads to a lower content of the residual amount of the cross-linking agent in solution.…”

New Methacrylated Biopolymer-Based Hydrogels as Localized Drug Delivery Systems in Skin Cancer Therapy

“…The extent of the bioadhesion depends on the free polymeric chains available for interlocking and crosslinking [50]. The presence of Aam and BisAam in the 3D networks forms tight crosslinked architectures; collapse or relaxation phenomena in the crosslinked hydrogels control the polymeric side chains that are available for entanglement with biological membranes and tissues, and therefore control the bioadhesion [51].…”