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Review
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Polymer implants for intratumoral drug delivery and cancer therapy
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Brent D. Weinberg 1, Elvin Blanco 2, Jinming Gao 2 *
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1Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, Ohio 44106
2Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75390
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*Correspondence to Jinming Gao, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75390. Telephone: 214-648-9278; Fax: 214-648-0264.
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biodegradable polymers • imaging methods • cancer chemotherapy • drug transport • controlled release • mathematical model • drug targeting
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To address the need for minimally invasive treatment of unresectable tumors, intratumoral polymer implants have been developed to release a variety of chemotherapeutic agents for the locoregional therapy of cancer. These implants, also termed polymer millirods, were designed to provide optimal drug release kinetics to improve drug delivery efficiency and antitumor efficacy when treating unresectable tumors. Modeling of drug transport properties in different tissue environments has provided theoretical insights on rational implant design, and several imaging techniques have been established to monitor the local drug concentrations surrounding these implants both ex vivo and in vivo. Preliminary antitumor efficacy and drug distribution studies in a rabbit liver tumor model have shown that these implants can restrict tumor growth in small animal tumors (diameter <1 cm). In the future, new approaches, such as three-dimensional (3-D) drug distribution modeling and the use of multiple drug-releasing implants, will be used to extend the efficacy of these implants in treating larger tumors more similar to intractable human tumors. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 1681-1702, 2008
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Received: 26 January 2007; Accepted: 17 April 2007
The study of polylactide and Polylactide-co-glycolide in the anti-cancer drugs delivery stem
The purpose of this study is to design the drug delivery system by using polylactide and poly (D, L-lactide-co-golycolide) as a polymeric matrix, and apply the devised to controlling the release of anticancer drugs. Research in this study has developed various drug delivery media by spray drying technique. The controlled release microspheres were prepared by spray drying and investigate several process parameters that can affect the characteristics of microspheres. Normal size distribution with diameters ranging from 1 to 10μm was obtained by spray drying technique. A higher yield of microspheres was recovered depending on polymer solution and process conditions employed. Results show that the yield of microspheres could reach 50% and the experimental drug loading approached to the theoretical drug loading. A factorial design approach was used to optimize conditions to produce microcapsules. The main factors affecting spray drying were found to be the initial temperature, polymer concentration and air flow. The in-vitro release of anticancer drug from microspheres sustained over seven days. Then we describe the water soluble anti-cancer drug, 5-Fluorouracil (5-FU) is encapsulated into biodegradable copoly (dl-lactic/glycolic acid)(PLGA) using spray drying method for the development of long-lasting controlled release systems. The mixture of dichloromethane/chloroform/methanol (1:1:2 v/v) resulted in the modification of morphology, while the physical structure of the microsphere varied from a porous PLGA microsphere to a dense PLGA microsphere. The results show that the average diameter was 2mm and anticancer drug loading of microspheres approached approximately 9 % (w/w). Encapsulation efficiency was reached up 90%，depending on the microsphere best formulation. In addition, the lactide/glycolide ratio of the polymer is an important parameter for controlling the release profile of the entrapped anticancer drug. Finally, the blood compatibility of PLA and PLGA samples were estimated in biocompatibility after prepared process. In use of the method of MTT assay, we could confirm the inhibiting proliferation of KB by the releasing anticancer drug and effective therapy to cancer in vitro.
Intracavitary chemotherapy (Gliadel®) for recurrent esthesioneuroblastoma: case report and review of the literature
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