HEPARIN-BASED NANOCOMPOSITES FOR BIOMEDICAL APPLICATIONS

Abstract

Nanomaterials usually lie in a similar size range of subcellular biomolecules/biomolecularcomplexes, and are comparatively smaller entities than a cell. Moreover, the built-in architecture of nanomaterials used in biomedical applications are also comparable to the bimolecular structures. Thereby, nanomaterials have been functionalized or encapsulated with biopolymers or biocompatible polymers to make them bioactive, biodegradable and perfect materials for drug delivery and targeting, medical devices, diagnosis and therapeutic applications. Owing to the greater surface-to-volume ratio, nanomaterials have higher surface functionalization capacity to be used in the formulation of potential therapeutic materials such as polymeric nanoparticles, lipid nanoparticles, metal nanoparticles, and various organic-inorganic hybrid nanoparticles. In this context, the polymers (both natural and synthetic polymers) play a pivotal role in maintaining the featured physicochemical characteristics of nanomaterials up to the application process. Polymers consist of long chains of smaller repeating monomeric units and uniformly distributed multiple charged functional groups over their backbone chain, enabling the molecular bridges between the nanomaterial and polymer. The addition of polymer to nanomaterial adds new dimensions of intrinsic properties to the nanomaterials such as improved stability, enhanced physical and mechanical properties, site-specific interactions, and systemic/smart delivery of nanomaterials. To obtain few of these properties, natural polymers such as proteins, polysaccharides, and polynucleic acids were given preference over synthetic polymers due to their natural abundance, enhanced biocompatibility, and ease of biodegradation. Among natural polysaccharide polymers, Glycosaminoglycans (GAGs) are a group of heterogeneous polysaccharides essentially present on cell surfaces, basement membranes, and extracellular matrix (ECM). GAGs alone or in conjunction with other biological macromolecules play potential biological roles in the body, which include: (1) conferring mechanical strength to the connective tissue; (2) regulating cell function; (3) vital during cell signaling events including wound healing, inflammation, and tissue injury/repair; (4) acting as mediators in the progression of inflammations/infections. GAG family comprises of heparin (HP), heparan sulfate (HS), dermatan sulfate (DS), keratin sulfate (KS), chondroitin sulfate (CS) and hyaluronic acid (HA). Heparin (HP) is the prime member of GAGs and a naturally occurring anticoagulant that is commonly found in all mammals and other vertebrates. It is 3-40 kDa, highly sulfated polydispersed GAGs that essentially retains a helical structure and associates with serglycin protein to display its antithrombotic activity. The linear chain of HP is mainly composed of 2-Osulfated L-iduronic acid and a mixture of either N- and 6-O-sulfated or N-acetylated Dglucosamine. Due to the ample sulfation in the polysaccharide chain, HP has the highest negative charge density (i.e. 2.7 sulfate groups per disaccharide) among all the available biomolecules. HP binds to blood coagulation cascade protein i.e., antithrombin (AT) which inhibits factor (FXa) and thrombin (FIIa) for fibrin formation. Principally, animal tissues such as the porcine intestine and bovine lung and intestine are used to extract and purify heparin as long-chain polymers called unfractionated heparins (UFHs).