Polymer blends as a route for controlled drug release

Controlled drug delivery is a growing multidisciplinary field of research that aims at developing methods to control the rate of the drug release into the body. For many years conventional drug formulations were used which involved a fast release of the active agent. With the development of more potent drugs, however, it became obvious that conventional therapeutic systems suffer from many drawbacks, including adverse side effects, fluctuation of drug levels in the body, poor drug efficacy, and poor patient compliance. The concentration, duration, and bioavailability of the pharmaceutical agents can not be controlled. Controlled release technology was anticipated to circumvent these problems. The goal of this technology is to maintain a therapeutic concentration of a drug in the body for a sustained period of time by releasing the agent in a predictable and controllable fashion. The term "Controlled drug delivery" covers a very wide range of techniques used to get therapeutic agents into the human body in a controlled manner. These techniques are capable of controlling the rate of drug delivery, sustaining the duration of therapeutic activity, and/or targeting the delivery of a drug to a specific tissue.;The objective of this project was to develop a novel polymer substrate satisfying the criteria of controlled release. We developed a new substrate preparation and drug encapsulation techniques, which have the potential to be applied in controlled drug delivery systems. We also studied surface modifications on polymer substrates, including internal surface modification using LBL technique and surface modification using a closed-cell method which extends the application possibilities for our porous substrate. Three different substrates with pores of different sizes were utilized to examine how pore size may affect the drug release profile.;The method used in this study to fabricate a co-continuous porous scaffold was performed by the melt blending of two immiscible polymers. The polymer substrate for drug release experiments was made by melt-blending of 3 different model blends; HDPE/SEB, HDPE/SEBS, and PLA/PS, followed by extraction of the porogen phase (SEB, SEBS, and PS). Polymer substrates with porosities above 94% were obtained.;The prepared sample was examined using SEM, BET, MIP and IA for internal surface area, average pore diameter, and microstructure. We obtained porous HDPE from HDPE/SEB with an average pore diameter of 0.32 mum and internal surface area of 13.72 m2/g, porous HDPE from HDPE/SEBS blend with an averaged pore diameter of 0.63 mum and internal surface area of 8.2 m2/g, and porous PLA from PLA/PS blend with an average pore size of 1.56 mum and internal surface area of 2.15 m2/g. BSA, a model drug, was loaded into these substrates following a vacuum-pressure protocol. Loading percentages with water of approximately 80% for HDPE substrates and 96% for PLA were obtained. BSA release tests were performed for all the samples using UV/Vis spectrophotometery. Two methods modification were used to improve the BSA release profile. First, samples were treated with 3 and 7 layers and in some cases 4 and 8 layers of polyelectrolytes to enhance their internal polymer surface properties, and consequently to increase the adhesion of the BSA molecules to the charged polymer surface. Second, closed-cell modification was applied to PLA (biodegradable sample) to form a drug holding layer, allowing more control over the release rate.;Polymers have been widely used to encapsulate drugs in the form of a reservoir or matrix in controlled release formulations. The active ingredient is either physically entrapped into the polymer matrix by an emulsification-, atomization-, or agitation-based process or it is linked to the polymer backbone via physical or chemical bonds. The drug release is typically observed to be diffusion controlled, polymer erosion controlled, or a combination of the two.;The structures prepared using our method, have the advantage of not being limited to one type of polymer system. Using this method, high void volume and high internal surface area are attainable. This method also allows a high level of control over the pore size (pore size ranging from microns to tenths of millimeters) and pore size distribution.