Drugreleasing polymer products

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A number of drugreleasing polymer products have been approved for clinical use (see Table 1), such as the Gliadel wafer which releases carmustine for localized treatment of glioblastoma multiforme in the brain (Brem and Gabikian, 2001). The number of products that combine a drug with a polymer or device is expected to increase significantly, which was a factor that motivated the recent establishment of the Office of Combination Products by the Food and Drug Administration. A variety of therapeutic agents can be encapsulated into polymeric release systems, including small molecule drugs, proteins, or even DNA encoding a protein of interest (Richardson et al., 2001a). Historically, the drug delivery

field has focused on the release of small molecule drugs for the treatment of disease. More recently, however, methodologies have been developed to release proteins and DNA from biomaterials, which expands the opportunities to direct physiological processes. This review provides background regarding the materials commonly utilized in sustained delivery and examines their applications relevant to neuroscience.

The number of products that combine a drug with a polymer or device is expected to increase significantly, which was a factor that motivated the recent establishment of the Office of Combination Products by the Food and Drug Administration.9

Polymers are now being used in developing advanced drug delivery systems as there has been seen to be great advances in polymer science.

Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition such as temperature, pH, and biomolecules.

Advances in polymer science have allowed the development of novel systems of drug delivery technology. Polymers are being used as these are said to enhance drug safety, efficacy and patient compliance.

Currently, many applications involving polyesters are being explored with polymers derived from monomers that are endogenous to the human metabolism. Examples of these monomers include glycerol, xylitol, sorbitol, and lactic, sebacic, citric, succinic, α-ketoglutaric, and fumaric acids.

The tissue response to an implant depends on a myriad of factors ranging from the chemical, physical and biological properties of the materials to the shape and structure of the implant. In the case of biodegradable biomaterials, their active biocompatibility must be demonstrated over time.

Elastomeric networks are increasingly being investigated for a variety of biomedical applications including drug delivery and tissue engineering. However, in some cases, their preparation requires the use of harsh processing conditions (e.g., high temperature), which limits their biomedical application. Herein, we demonstrate the ability to form elastomeric networks from poly(glycerol-co-sebacate) acrylate (PGSA) under mild conditions while preserving a wide range of physical properties.

The development of biodegradable elastomers has increasingly become important in biomedical applications. Elastomers have gained popularity because they can provide stability and structural integrity within a mechanically dynamic environment without irritation to the hosting tissues while they exhibit mechanical properties similar to those of soft tissues. Biodegradable elastomers can be important materials for a wide variety of medical applications including drug delivery and tissue regeneration, where (cell-seeded) constructs are designed to aid or replace damaged or diseased tissue.2-4 Examples of applications for elastomeric biodegradable biomaterials are small-diameter vascular grafts and nerve conduits.

Aliphatic polyesters, due to their favorable features of biodegradability and biocompatibility, constitute one of the most important classes of synthetic biodegradable polymers and are nowadays available commercially in a variety of types. Most of these polyesters have been studied for their biocompatibility, bioresorbability and their cytocompatibility as well [5, 6]. It was found that they are biocompatible materials with higher hydrolysability into human body and therefore they can be used as drug carriers for controlled release devices and for biomedical applications. Targeting drug delivery systems have been studied widely in cancer therapeutic applications [7-11]. In the last years poly(alkylene dicarboxylates) such as poly(propylene succinate) (PPSu) and poly(propylene adipate) (PPAd) have been synthesized and studied [12-19]. These polyesters are appropriate for medical and biomedical applications including drug delivery systems by preparing drug loaded nanoparticles or solid dispersions. Only a few studies have been reported so far for the preparation of nanoparticles and solid dispersions for drug delivery systems using such aliphatic polyesters.

Delivery systems Polymeric delivery systems have the potential to (i) maintain therapeutic levels of a drug, (ii) reduce harmful side effects, (iii) decrease the amount of the molecule required, (iv) decrease the number of dosages, and (v) facilitate the delivery of drugs with short in vivo half-lives (Langer, 1998). Currently, the most common method to deliver therapeutic factors to the CNS involves surgically implanting pump or cannula systems (Harbaugh et al., 1988). However, pumps frequently become clogged within a few days, which limits their ability to sustain effective concentrations (Jones and Tuszynski, 2001). Furthermore, the molecule is maintained in an aqueous reservoir, which is not suitable for therapeutic agents with short half-lives.

Polymeric encapsulation can protect the incorporated drug from degradation by the surrounding aqueous environment, We recently created a tough biodegradable elastomer, poly(glycerol sebacate) (PGS), which features robust mechanical properties and in vitro and in vivo biocompatibility. However, harsh conditions (>80 °C, <5 Pa) and long reaction times (typically >24 h) are required for its curing and thus limit its ability to polymerize directly in a tissue or to incorporate cells or temperature-sensitive molecules. As such, there is an unmet need to develop alternative processing strategies to overcome the limitations of thermally processing PGS. One convenient strategy is the implementation of photopolymerization. This technique has been utilized for several decades in biomedical research and has become an integral method for in situ delivery of resins in the practice of dentistry. Recently, there has been great interest in using photopolymerization techniques to prepare polymeric networks for tissue engineering applications as well as for minimally invasive medical procedures. To this end, acrylate groups have been included in polymers for participation in chemical cross-linking between polymer chains by photoinduced free radical polymerization.11,20-22

In this paper, we describe the synthesis and characterization of a photocurable polymer based on the chemical modification of PGS with acrylate moieties (designated poly(glycerol sebacate) acrylate, or PGSA). PGSA can be cured rapidly (within minutes) at ambient temperatures to form polymeric networks with a wide range of mechanical properties and in vitro enzymatic degradation and hydrolysis profiles. Incorporation of poly(ethylene glycol) diacrylate (PEG-DA) allowed for additional control of mechanical properties and swelling ratios in an aqueous environment. Initial experiments with photocured PGSA networks demonstrated in vitro biocompatibility by sufficient cell adherence and subsequent proliferation into a confluent cell monolayer.

Langer 2007

Polymers in drug delivery

Omathanu Pillai and Ramesh Panchagnula

Delivery systems for small molecule drugs, proteins, and DNA:

the neuroscience/biomaterial interface

Kevin J. Whittleseya,*, Lonnie D. Shea

Devin G. Barrett and Muhammad N. Yousaf Molecules 2009, 14, 4022-4050