Evaluation of the action of topical use of heparin encapsulated in polymeric nanoparticles coated chitosan in model of skin ulcer in rats

Abstract

The ulcers are a complication of various diseases such as diabetes, deep vein thrombosis (DVT), sickle cell anemia, among others and have a high rate of incidence. This increase brings a decline in quality of life of patients, causing pain, discomfort and limited mobility and could lead to loss of limb in cases of gangrene. Topical treatment of ulcers and other skin wounds has been widely used because it is not invasive and allows the drug absorbed can act in the absence of hepatic metabolism, but has certain limitations because it has natural barriers, mainly represented by the stratum corneum. These limitations can be minimized with the use of biocompatible and biodegradable nanoparticles as carriers of drugs, thus having a proper absorption through the skin, since due to its small size, this passage becomes more effective and is accomplished mainly through the route via pores. The objective of this project is the pharmaceutical preparation for topical administration of heparin in sustained release systems, aiming at the biological potential of this drug encapsulated in polymeric nanoparticles coated with chitosan. For this to be prepared nanoparticles of poly (e-caprolactone) coated with chitosan by the method of emulsification and solvent evaporation. The particles will be characterized for morphology by microscopic techniques, size and zeta potential by photon correlation spectroscopy and in vitro release. Furthermore, topical formulations of these particles will be prepared and applied to wounds incurred in normal rats and rats with type I diabetes mellitus induced. Parameters such as oxidative stress, histological, macroscopic evaluation of injuries and imuhistoquímica are used in the evaluation during and after the healing of ulcers in animals. In this project it is expected that the combination of the properties of low molecular weight heparin (LMWH) such as analgesia, decreased edema and erythema, neoangiogenesis and epithelial healing, with the properties of chitosan, which has healing activity, and mucoadhesive antimicrobial, promote a greater effectiveness in wound healing in normal rats and rats with diabetes mellitus type I. (AU)