In Vitro Controlled Drug Release of Anticancer Drugs
Deguelin and Cisplatin by Lauric Acid
Derived Polyanhydride as Carrier
John Marty Mateo1 and Florentino C. Sumera*
1Natural Sciences Research Institute, University of the Philippines,
Diliman, Quezon City, 1101, Philippines
*Institute of Chemistry, University of the Philippines,
Diliman, Quezon City,1101, Philippines
New lauric acid derived polyanhydride was used in wafer form as carrier in the study of drug release of two anticancer drugs. Its degradation and drug release behavior was herein studied in phosphate buffer solution at pH 7.4 and 37o C. Anticancer drugs deguelin and cisplatin were loaded into wafers made of the new polyanhydride, poly(sebacic acid–co-hydroxylauric acid maleate) anhydride for controlled drug release studies and comparison. The polyanhydride showed that it is degradable, biocompatible and non cytotoxic. Using poly(sebacic acid–co-hydroxylauric acid maleate) anhydride wafers containing 5% deguelin, the device can provide a controlled release of deguelin in 20 days delivering 84.6% cumulative release of the drug while following a zero order model of release kinetics. Similarly the device can also provide a controlled release of cisplatin in 7 days delivering 71.22% cumulative release of the drug following also a zero order model of release kinetics. The mechanism of both drug releases was determined to be by diffusion. This drug-loaded polyanhydride system could find application in localized treatment such as in decreasing tumor size, in preventing tumor recurrence or in post-operative cancerous tumor extraction.
Currently drugs combined with polymeric carriers are being developed for controlled release to replace drugs which have short uncontrolled release profile. They are being developed to control drug release with fewer doses for localized treatment that avoids toxicity associated with systemic drug delivery. Among these polymeric drug delivery systems are the polyanhydrides which have been studied in detail over the past few decades. Polyanhydrides as drug carriers have many desirable characteristics that made them a good choice for drug delivery. For example they surface erode in media, rather than erode in bulk, ultimately controlling drug release rates (Johnson 2008).
Although a variety of polymer structures have already been reported since the discovery of polyanhydrides, the most important type used are the aliphatic polyanhydrides (Jain et al. 2005) .These polyanhydrides are biodegradable, due mainly to their anhydride linkages, and highly biocompatible, unlike the aromatic types, that made this group of polymers an excellent material . . . . read more
DAGBAY K, SUMERA FC. 2014. Lauric acid derived polyanhydrides: Synthesis, characterization, in vitro degradation and drug release behaviour. Philippine Journal of Science 143 (2): 113-123.
DANG W, DAVIAU T, YING P, et al. 1996. Effects of GLIADEL wafer initial molecular weight on the erosion of wafer release of BCNU. J Control Rel 42:83-92
DASH S, MURTHY PN, NATH L, CHOWDHURY P. 2010. Kinetic modelling on drug release from controlled drug delivery systems. Acta Poloniae Pharmaceutica - Drug Research 67 (3): 217 – 223.
DOMB AJ, NUDELMAN R. 1995. Biodegradable polymers derived from natural fatty acids. Journal of Polymer Science: Part A: Polymer Chemistry 33: 717-725.
JAIN JP, MODI S, DOMB AJ, KUMAR N. 2005. Role of polyanhydrides as localized drug carriers. Journal of Controlled Release 103(3): p. 541-563.
JAIN JP, MODI S, KUMAR N. 2008. Hydroxy fatty acid based polyanhydride as drug delivery system: Synthesis, characterization, in vitro degradation, drug release, and biocompatibility. Journal of Biomedical Materials Research Part A 84: 740–752.
JIAN W, FANG F Y, GAN C, WU Y, PANG J. 2009. Extraction and purification of deguelin from Derris trifoliata Lour root. Int J Agric & Biol Eng 2(4): 98-103.
JOHNSON ML. 2008. Polyanhydride blends as drug delivery matrices to control biofilms, bone and nerve regeneration. [PhD Thesis]. Rutgers, the State University of New Jersey, 150p.
MOSMANN T. 1983. Rapid colorimetric assay for cellular growth and survival. J Immunol Methods 65 (1) 55 – 63.
RITGER PL, PEPPAS NA. 1987. A simple equation for description of solute release. I. Fickian and non Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. Journal of Controlled Release 5: 23 – 26.
ROSEMAN TJ, HIGUCHI WI. 1970. Release of methoxyprogesterone from silicone polymer. Journal of Pharmaceutical Sciences 59: 353 – 357
SAMPATH P, BREM H. 1998. Implantable Slow release therapeutic polymers for the treatment of malignant brain tumors. J. Moffitt Cancer Center 5 130 – 137.
SCKOWICZ D, ABTEW E, KHAN W, COOLOVANEVSKI L, STEIMAN NOAM, WEINIGER F, DOMB AJ. 2015. Journal of Compatible Polymers: Biomedical Applications 0883911515598796
SHIKANOV A, EZRA A, DOMB AJ. 2005. Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel-effect of additives. Journal of Controlled Release 105(1): p.52-67.
SHIKANOV A, SHIKANOV S, VAISMAN B, GOLENSER J, DOMB AJ. 2011. Cisplatin tumor biodistribution and efficacy after intratumoral injection of a bio-degradable extended release implant. Chemotherapy Research and Practice Vol. 2011, Article ID 175054, 9 p.
TAMADA JA, LANGER R. 1993. Erosion kinetics of hydrolytically degradable polymers. Proc Natl Acad Sci USA 90: 552 – 556. Chemistry..
TEOMIN D, DOMB AJ. 2001. Nonlinear Fatty acid terminated polyanhydrides. Biomacromolecules 2: 37-44.
TEOMIN D, NYSKA A, DOMB AJ. 1999. Ricinoleic acid–based biopolymer. Journal of Biomaterials Research 45: 258-267.
TEOMIN D, MÄDER K, BENTOLILA A, MAGORA A, DOMB AJ. 2001 .γ-Irradiation of Saturated and Unsaturated Aliphatic Polyanhydrides-Ricinoleic Acid Based Polymers, Biomacromolecules 2: 1015 -1022.
TAN H, SHUAI T. 1997. Synthesis and properties of biodegradable copolymers based on polyether oligomers and fatty acids. J Appl Poly Sci 66: 1891-1898.
VERMA RS, BABU A. 1995. Human chromosomes:Principles and techniques. 2nd ed. McGraw Hill, Inc. USA. p 9-10.
WU C, FU J, ZHAO Y. 2000. Novel nanoparticles formed via self-assembly of poly(ethylene glycol-b-sebacic anhydride) and their degradation in water. Macromolecules 33: 9040 - 9043.