Final Report Summary - BIOTRANSOS (Design and evaluation of a bioadhesive film with easy peeling properties for transdermal drug delivery: application for osteoporosis treatment)
Transdermal drug delivery (TDD) system is a competing pharmaceutical market for which improvement of existing systems in adequation with patient willing is a determining aspect.
TDD systems, commonly called patches, deliver the therapeutic agent, when applied to the skin, at a controlled rate through the skin to the systemic circulation and to the target organs. Transdermal drug delivery systems, as compared to their corresponding classical oral and injectable dosage form counterparts offer many advantages, but also certain limitations. The most relevant adverse effects of transdermal therapy are skin irritation effects due to the presence of adhesives. Another disadvantage of transdermal drug-delivery system as compared to other controlled release formulations is its high cost due to the use of synthetic polymer.
The originality of the BIOTRANSOS project is reflected in the use of biocompatible natural polymer for the elaboration of the bioadhesive film and the specific surface modification processes for achievement of the desired surface characteristics (adhesion and easy skin removal properties). The functionalization of the biocompatible drug loaded matrix by grafting a thermo-responsive polymer (poly-isopropylacrylamide: PNiPAAm) would allow to introduce a ‘switch’ mechanism on the surface for an easy removal on demand. We expect that the surface modified film presents significant reduced peel strength at low temperature due to the hydrophobic/hydrophilic nature of PNiPAAm depending on the temperature (figure 1).
Thus, the overall goal of BIOTRANSOS project is to design and evaluate a new transdermal device, containing a natural biocompatible matrix with conventional hydrogel properties, but with advanced stimuli responsiveness properties.
To achieve this objective, four main elements were integrated in the project work plan, being disclosed in four Work Packages (WP). Figure 2 summarizes the global strategy used in this project.
First we studied the preparation and characterization of films using different biocompatible polymers (hydroxypropyl methylcellulose, hydroxymethyl cellulose, alginate, chitosan..) in order to select the polymer presenting the best film forming and mechanical properties. Chitosan based film presenting the best characteristics; we worked on the improvement of its ductibility and resistance by studying the incorporation of plasticizers into the formulation. Then we tried to enhance skin adhesion properties either by (1) adding commercial Pressure Sensitive Additive (PSA) polymer; or (2) by incorporation of polyacrylic acid. Adhesives properties were analyzed with a tack test.
During the second work package we studied the coating of the superior surface of chitosan film with hydrophobic components in order to create a backing layer with occlusive property. We worked the development of new green coatings made from fatty acid or derivatives dispersions. Contact angle measurements, water vapor permeability and scanning electronic microscopic images were used to characterize the coatings. The barrier properties found for the chitosan film with and without coatings were compared with a commercial patch.
Incorporation of a switch mechanism on the surface of chitosan film in contact with skin was achieved in the third WP by grafting PNiPAAm by two different methods: (a) by UV grafting; (b) using plasma treatment activation. We studied the surface film modification with a continuous layer and discontinuous coating involving microgel incorporation. In order to determine the best strategy of incorporation, films surface were analyzed by SEM, AFM, XPS.
Finally, in vitro drug release studies were done in order to determine the influence of the surface modification on release properties of chitosan film. In vitro release kinetics were studied (WP4) by two different methods from chitosan films before and after surface modification: (1) using the dissolution test for transdermal delivery systems described in European Pharmacopoeia; (2) using Franz-diffusion cells, with synthetic membranes as skin model.
The work carried out throughout the BIOTRANSOS project has led to significant outcomes, for both fundamental and applied research. The main highlights in our sense are the following:
• First and foremost, the preparation of biocompatible film using the adequate hydrogel blend
• The determination of the best strategies to incorporate PNiPAAm, a thermo-sensitive polymer onto chitosan film surface
• The study the influence of surface modifications on drug release properties of chitosan film.
Research on the work initiated during the BIOTRANSOS is being continued at the CIRIMAT Institute in Toulouse. The results already obtained allowed the Fellow to develop two news research projects:
• The development of new biomaterials for skin disease treatment (dermatology application)
• The design on biopolymers based film for surgery applications.
Researchers to contact for further details about the project:
Dr Audrey Tourrette (audrey.tourrette@univ-tlse3.fr )
Dr Sophie Cazalbou (sophie.cazalbou@univ-tlse3.fr )