THERAPEUTIC SUPRAMOLECULAR NETWORKS INTEGRATING CASEIN MICELLES FOR CONTROLLED TOPICAL DRUG DELIVERY

BONAFE JUAN CRUZ; AMBROSIONI, FRANCO E.; PICCHIO, MATÍAS L.; JIMÉNEZ KAIRUZ, ÁLVARO F.

Simposio; XIII SIMPOSIO ARGENTINO DE POLÍMEROS 2019; 2019

The healing process of infected skin wounds take longer thannon-infected wounds ones. Many antibiotics as silversulfadiazine (SSD) may be used to prevent and heal infections.However, their hydrophobicity results in several problemsincluding low solubility, low stability and skin penetration.The development of nanocarriers has enhanced the efficacy ofdrug delivery which allowed overcoming those obstacles.Specifically, novel drug delivery systems based onnanoparticles bulid from biopolymers like proteins are beingdeveloped due to their biocompatibility and biodegradability.Bovine casein is a family of proteins normally found in milk andpossesses a wide spectrum of structural and physicochemicalproperties which make them appropriate for nanocarriersengineering. In presence of calcium, these proteins tend toself-assemble into micelles with an average diameter of 180nm. Besides to being biocompatibility, casein micelles (CM)could be readily degraded by enzymes like matrixmetalloproteinases (MMPs) which are present in both acuteand chronic wounds..On the other hand, supramolecular gels are an emergent classof dynamic materials formed mainly by non-covalent andreversible intermolecular interactions which enable the easymodification of their physical properties. The integration oftherapeutics nanoparticles in this kind of materials could opennew opportunities in topical drug delivery for wound healingapplications. For example, the use of thermo-responsivesupramolecular hydrogels could allow an easy application overthe affected area while it is still in a liquid state and gellingonce the wound is covered.In this regard, polyvinyl alcohol (PVA), a biocompatible andharmless polymer widely used in pharmaceuticals, has a greatpotential to prepared supramolecular hydrogels by hydrogenbonding interactions PVA is a water soluble material formed bylong carbonated chains with a large amount of hydroxyl groupscapable of generating hydrogen bonds between each otherand with another hydroxylated compounds. Recently, ourgroup has found that small plant-derived phenolic compounds(PCs) can effectively assist the supramolecular assembly ofPVA into thermo-reversible hydrogels. Among the PCsexplored as physical crosslinker, pyrogallic acid (PGA),apolyhydroxybencene used in medicine as antioxidant,antimicrobial and anti-inflammatory, showed superior PVAbinding ability. PGA structure presents 3 hydroxyl groups thatcan interact with PVA by hydrogen bonds to formsupramolecular networks. Thus, the aim of this work waspreparing PVA/PGA supramolecular networks integrating SSDloaded-crosslinked casein micelles (CCM) for their applicationas topical drug delivery system in wound healing.Trihydroxybenzoic acid (gallic acid) was used to modify theCCM aiming to improve their dispersibility into thesupramolecular matrix. These nanoparticles-containingsupramolecular materials could be applied in liquid state at37°C on the damaged zone and then, in situ gelation can occurat the skin temperature (33 °C). The supramolecular binder,PGA can act as therapeutic drug due to their anti-inflammatory and antibacterial properties. The controlled diffusion of PGAfrom the supramolecular matrix to the injury changes theviscoelastic properties of the network which could trigger therelease of the SSD-loaded CCM. Then, the CCM can bedegraded by the presence of MMPs and specifically release thepharmaceutical molecule at wound site.