The development of polyanhydrides for drug delivery applications.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
Journal of Biomaterials Science Polymer Edition (Impact Factor: 1.7). 02/1992; 3(4):315-53. DOI:10.1163/156856292X00402
Source: PubMed

ABSTRACT This paper reviews the development of the polyanhydrides as bioerodible polymers for drug delivery applications. The topics include design and synthesis of the polymer, physical properties, techniques to fabricate the polymer into drug delivery devices, evaluation of biocompatibility, and example applications of the polyanhydrides. Discussion of the interrelationship between the physical-chemical properties of the polyanhydrides, fabrication methods, and drug release rates is included. One section is devoted to a case study to provide a historical perspective of the development a polyanhydride-based drug delivery treatment from the conception of the idea to the final stages of human clinical trials. This section includes an outline of the extensive in vitro and in vivo testing that is necessary for development of a new material for biomedical applications.

0 0
  • [show abstract] [hide abstract]
    ABSTRACT: Novel drug delivery systems capable of continuous sustained release of therapeutics have been studied extensively for use in the prevention and management of chronic diseases. The use of these systems holds promise as a means to achieve higher patient compliance while improving therapeutic index and reducing systemic toxicity. In this work, an implantable nanochannel drug delivery system (nDS) is characterized and evaluated for the long-term sustained release of atorvastatin (ATS) and trans-resveratrol (t-RES), compounds with a proven role in managing atherogenic dyslipidemia and promoting cardioprotection. The primary mediators of drug release in the nDS are nanofluidic membranes with hundreds of thousands of nanochannels (up to 100,000/mm(2)) that attain zero-order release kinetics by exploiting nanoconfinement and molecule-to-surface interactions that dominate diffusive transport at the nanoscale. These membranes were characterized using gas flow analysis, acetone diffusion, and scanning and transmission electron microscopy (SEM, TEM). The surface properties of the dielectric materials lining the nanochannels, SiO(2) and low-stress silicon nitride, were further investigated using surface charge analysis. Continuous, sustained in vitro release for both ATS and t-RES was established for durations exceeding 1 month. Finally, the influence of the membranes on cell viability was assessed using human microvascular endothelial cells. Morphology changes and adhesion to the surface were analyzed using SEM, while an MTT proliferation assay was used to determine the cell viability. The nanochannel delivery approach, here demonstrated in vitro, not only possesses all requirements for large-scale high-yield industrial fabrication, but also presents the key components for a rapid clinical translation as an implantable delivery system for the sustained administration of cardioprotectants.
    Analytical and Bioanalytical Chemistry 10/2012; · 3.66 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: In order to develop degradable elastomers with a satisfactory combination of flexibility and enzyme-mediated degradation rate, the mechanical properties, enzymatic degradation kinetics and biocompatibility of poly(xylitol sebcate) (PXS) has been systematically investigated in comparison with poly(glycerol sebacate) (PGS). Under the same level of crosslinked density, the PXS elastomer networks have approximately twice the stretchability (elongation at break) of their PGS counterparts. This observation is attributable to the relatively longer and more orientable xylitol monomers, compared with glycerol molecules. Although xylitol monomers have two more hydroxyl groups, we, surprisingly, found that the hydrophilic side chains did not accelerate the water attack on the ester bonds of the PXS network, compared with their PGS counterpart. This observation was attributed to a steric hindrance effect, i.e. the large-sized hydroxyl groups can shield ester bonds from the attack of water molecules. In conclusion, the use of polyols of more than three -OH groups is an effective approach enhancing flexibility, whilst maintaining the degradation rate of polyester elastomers. Further development could be seen in the copolymerization of PPS with appropriate thermoplastic polyesters, such as poly(lactic acid) and polyhydroxyalkanoate.
    Biomedical Materials 04/2013; 8(3):035006. · 2.17 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01M NaOH for 5min and acidification with 0.01M HCl for 25s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells.
    Materials science & engineering. C, Materials for biological applications. 10/2013; 33(7):3677-87.

J A Tamada