(162c) Simvastatin Release from Alginate Bilayer Membranes for Wound

Alginate is a polysaccharide obtained mainly in two ways: bacterial synthesis or extraction from brown seaweeds, as the Laminaria Hyperborea, Ascophyllumnodosun, and Macrocystispryiferas species. This polymer has some essential properties, such as biocompatibility, low cost, and healing characteristics, that can be useful as a matrix for wound dressing. To aggregate new healing functionality on alginate dressings, some pharmaceutical molecules have been introduced to produce bioactive dressings. Simvastatin is a statin that acts by inhibiting hydroxymethylglutaryl coenzyme A reductase and is commonly used as a hypocholesterolemic agent in cardiovascular diseases. Recently, the anti-inflammatory, antithrombogenicity, antioxidant and restorative effects have been investigated, showing as a promising drug for dermal treatment. Most of the wound dressing on the market is produced as a single layer device. Multilayer wound dressing might offer an essential alternative due to the possibility of modulating the release of drugs by modifying the drug diffusion rate in the device, in the function of multiple polymeric barriers created, with different chemical or physical properties. This study aimed to produce and characterize three types of alginate membranes: the first one is a single dense alginate membrane, the second is a dense bilayer alginate membrane. Each membrane with a specific crosslinking rate and the third one is bilayer membrane, where one layer is dense and another is porous (obtained by freeze-drying). The membranes were characterized by weight, thickness, surface pH, infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM) and water vapor transmission rate (WVTR). The difference in the crosslinking degree (bottom and top layers) influenced the membrane’s morphology and consequently, in their physical barrier properties. Comparing the two types of bilayer films, it was observed that the higher crosslinking degree influenced the weight more significantly since the increase in the interconnection between the polymer chains become the membrane more rigid and heavy.

On the other hand, the freeze-drying process influenced more significantly the thickness. The pH of the surface of the films showed a positive value, 6.6 in distilled water, useful for application as a wound dressing, not causing irritation to the skin, and enhancing the healing process. From the SEM results, it can be seen that the films presented a rough surface, increasing the contact surface area of the film with the skin. The absence of pores in the dense membranes is useful to prevent the direct penetration of microorganisms into the wounds (top layer) and the presence of a porous layer is important for exudate absorption. The FTIR results showed the characteristic peaks of alginate-based materials. The WVPR values for bottom, top and double layer alginate membranes were 2981.80 ± 82.96, 2335.45 ± 233.58, and 2518.25 ± 152.57 g/m².24h, respectively. The results of WVPR are higher in the lower layer due to a weak hydrophobic interaction in that layer. The bilayer alginate membranes, produced by the superposition of a top layer on the bottom layer, presented an intermediate WVPR value, showing that in addition to the higher thickness, the void space between the layers can be a useful parameter to modify the WVPR. The WVPR values for porous and freeze-dried bilayer membranes were 3694.6 ± 243.57 and 2708.6 ± 920.9 g / m².24h, respectively. WVPR was also studied for alginate membranes loaded with simvastatin, in which it was observed that simvastatin addition decreased WVPR, probably due to the hydrophobic characteristics of simvastatin, reducing the hydrophilicity of the membranes. The films demonstrated good reproducibility with potential applications for wound dressings.