THERAPEUTIC SUPRAMOLECULAR NETWORKS INTEGRATING CASEIN MICELLES FOR CONTROLLED TOPICAL DRUG DELIVERY

Congreso; XIII SIMPOSIO ARGENTINO DE POLÍMEROS 2019; 2019

The healing process of infected skin wounds take longer than non-infected wounds ones. Many antibiotics as silver sulfadiazine (SSD) may be used to prevent and heal infections. However, their hydrophobicity results in several problems including low solubility, low stability and skin penetration.The development of nanocarriers has enhanced the efficacy of drug delivery which allowed overcoming those obstacles. Specifically, novel drug delivery systems based on nanoparticles bulid from biopolymers like proteins are being developed due to their biocompatibility and biodegradability. Bovine casein is a family of proteins normally found in milk and possesses a wide spectrum of structural and physicochemical properties which make them appropriate for nanocarriers engineering. In presence of calcium, these proteins tend to self-assemble into micelles with an average diameter of 180 nm. Besides to being biocompatibility, casein micelles (CM) could be readily degraded by enzymes like matrix metalloproteinases (MMPs) which are present in both acute and chronic wounds.. On the other hand, supramolecular gels are an emergent class of dynamic materials formed mainly by non-covalent and reversible intermolecular interactions which enable the easy modification of their physical properties. The integration of therapeutics nanoparticles in this kind of materials could open new opportunities in topical drug delivery for wound healing applications. For example, the use of thermo-responsive supramolecular hydrogels could allow an easy application over the affected area while it is still in a liquid state and gelling once the wound is covered.In this regard, polyvinyl alcohol (PVA), a biocompatible and harmless polymer widely used in pharmaceuticals, has a great potential to prepared supramolecular hydrogels by hydrogen bonding interactions PVA is a water soluble material formed by long carbonated chains with a large amount of hydroxyl groups capable of generating hydrogen bonds between each other and with another hydroxylated compounds. Recently, our group has found that small plant-derived phenolic compounds (PCs) can effectively assist the supramolecular assembly of PVA into thermo-reversible hydrogels. Among the PCs explored as physical crosslinker, pyrogallic acid (PGA),a polyhydroxybencene used in medicine as antioxidant, antimicrobial and anti-inflammatory, showed superior PVA binding ability. PGA structure presents 3 hydroxyl groups that can interact with PVA by hydrogen bonds to form supramolecular networks. Thus, the aim of this work was preparing PVA/PGA supramolecular networks integrating SSD loaded-crosslinked casein micelles (CCM) for their application as topical drug delivery system in wound healing. Trihydroxybenzoic acid (gallic acid) was used to modify the CCM aiming to improve their dispersibility into the supramolecular matrix. These nanoparticles-containing supramolecular materials could be applied in liquid state at 37°C on the damaged zone and then, in situ gelation can occur at the skin temperature (33 °C). The supramolecular binder