In Vitro Studies On The Release Of Isoniazid Incorporated In Poly(ε-caprolactone)

A polymeric micro- and nanosphere formulation using poly (ε-caprolactone) (PCL) to entrap an antituberculosis drug, isoniazid (INH), was developed and characterized. The microspheres were prepared by a solvent evaporation method using ethyl acetate, PCL and INH as the organic phase and water and Tween 40 as the aqueous phase. The nanospheres were prepared by a spontaneous emulsification solvent diffusion method using 40% ethanol in acetone (v/v), PCL and INH as the organic phase and water and Tween 40 as the aqueous phase. After freeze-drying, these systems were characterized by scanning electron microscopy (SEM), particle size analysis, determination of entrapped INH content, in vitro INH release and brine shrimp toxicity bioassay. © E.S.I.F.T. srl.185473479Fauci, A.S., Infectious diseases: Considerations for the 21st century (2004) Clin Infect Dis, 32, pp. 675-685Espinal, M.A., Kim, S.J., Suarez, P.G., Standard short-course chemotherapy for drug-resistant tuberculosis: Treatment outcomes in 6 countries (2000) JAMA, 283, pp. 2537-2545Khuller, G.K., Pandey, R., Sustained release drug delivery systems in management of tuberculosis (2003) Indian J Chest Dis Allied Sci, 45, pp. 229-230Dutt, M., Khuller, G.K., Liposomes and PLG microparticles as sustained release antitubercular drug carrier - An in vitro-in vivo study (2001) Inter J Antimicrob Agents, 18, pp. 345-1252Dutt, M., Khuller, G.K., Chemotherapy of Mycobaterium tuberculosis infections in mice with a combination of isoniazid and rifampin entrapped in poly (DL-lactide-co- glycolide) microparticles (2001) J Antimicrob Chemother, 47, pp. 829-835Ul-Ain, Q., Sharma, S., Khuller, G.K., Chemotherapeutic potential of orally administered poly (lactide-co-glycolide) microparticles containing isoniazid, rifampin, and pyrazinamide against experimental tuberculosis (2003) Antimicrob Agents Chemother, 47, pp. 3005-3007Ul-Ain, Q., Sharma, S., Khuller, G.K., Garg, S.K., Alginate-based oral drug delivery system for tuberculosis: Pharmacokinetics and therapeutic effects (2003) J Antimicrob Chemother, 51, pp. 931-938Silva, R.M.L., Evangelista, R.C., Microspheres of alginate-chitosan containing isoniazid (2003) J Microencapsul, 20, pp. 145-152Sharma, R., Saxena, D., Dwivedi, A.K., Misra, A., Inhalable microparticles containing drug combination to target alveolar macrophages for treatment of pulmonary tuberculosis (2001) Pharm Res, 18, pp. 1405-1410Zhou, H.Y., Lengsfeld, C., Claffey, D.J., Ruth, J.A., Hybertson, B., Randolph, T.W., Ng, K.Y., Manning, M.C., Hydrophobic ion pairing of isoniazid using a prodrug approach (2002) J Pharm Sci, 91, pp. 1502-1511Dutt, M., Khuller, G.K., Therapy efficacy of poly (DL-lactide-co-glycolide)-encapsulated antitubercular drugs against Mycobaterium tuberculosis infections in mice (2001) Antimicrob Agents Chemother, 45, pp. 363-366Dutt, M., Khuller, G.K., Sustained release of isoniazid from a single injectable dose of poly (DL-lactide-co-glycolide) microparticles as a therapeutic approach towards tuberculosis (2001) Intern J Antimicrob Agents, 17, pp. 115-122Durán, N., De Oliveira, A.F., De Azevedo, M.M.M., Production of micro and nanospheres of polycaprolactone in the isoniazid encapsulation as antimycobacterial agents (2002), Brazilian Patent-PIBr 2000204125. Derwent Number, 2004-571899 [56]Anisimova, Y.V., Gelperina, S.I., Peloquin, C.A., Heifets, L.B., Nanoparticles as antituberculosis drugs carrier: Effect on activated against Mycobcterium tuberculosis in human monocyte-derived macrophages (2000) J Nanoparticle Res, 2, pp. 165-171. , 2000Pandey, R., Sharma, A., Zahoor, A., Sharma, S., Khuller, G.K., Prasad, B., Poly (DL-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis (2003) J Antimicrob Chemother, 52, pp. 981-986Pandey, R., Zahoor, A., Sharma, S., Khuller, G.K., Nanoparticles encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis (2003) Tuberculosis, 83, pp. 373-378Sharma, A., Sharma, S., Khuller, G.K., Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carrier for treatment of tuberculosis (2004) J Antimicrob Chemother, 54, pp. 761-766Dutt, M., Khuller, G.K., Sub-cutaneous nanoparticles-based antitubercular chemotherapy in an experimental model (2004) J Antimicrob Chemother, 54, pp. 266-268Mei, N., Chen, G., Zhou, P., Chen, X., Shao, Z.-Z., Biocompatibility of poly (ε-caprolactone) scaffold modified by chitosan - The fibroblasts proliferation in vitro (2005) J Biomat Appl, 19, pp. 323-339Pitt, C.G., (1990) Biodegradable Polymers as Drug Delivery System, p. 710. , M. Chasin R. Langer (Eds.), Dekker, New YorkSinha, V.R., Bansal, K., Kaushik, R., Kumria, R., Trehan, A., Poly-ε-caprolactone microspheres and nanospheres: An overview (2004) Intern J Pharm, 278, pp. 1-23Perez, M.H., Zinutti, C., Lamprecht, A., The preparation and evaluation of poly (ε-caprolactone) microparticles containing both lipophilic and hydrophilic drug (2000) J Control Release, 65, pp. 429-438Goldstein, J., Newburg, D.E., Joy, C., (2003) Scanning Electron Microscopy and X-Rays Micro Analysis, p. 675. , Springer Sci. N.Y., USAStine, K.J., Knobler, C.M., Fluorescence Microscopy - A tool for studying the physical-chemistry of interfaces (1992) Ultramicroscopy, 47, pp. 23-34O'Donnell, P.B., McGinity, J.W., Preparation of microspheres by the solvent evaporation technique (1997) Advanced Drug Delivery Rev, 28, pp. 25-42Murakami, H., Kobayashi, M., Takeuchi, H., Kawashima, Y., Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles (2000) Powder Technol, 107, pp. 137-143Mc Laughin, J.L., Colman-Saizarbitoria, T., Anderson, J.E., Three simple bioassays for natural chemical products (1995) Rev Soc Venezolana Quim, 18, pp. 13-18Sam, T.W., Toxicity testing using the brine shrimp: Artemia salina (1993) Ioactive Natural Products: Detection, Isolation ans Structural Determination, pp. 491-1454. , Ed. SM Colegate CRC Press Inc. :Ch. 18Ha, J.-H., Kim, S.-H., Han, S.-Y., Albumin release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(e-caprolactone) and poly(ethylene glycol) macromer (1997) J Control Release, 49, pp. 253-262Armani, D.K., Liu, C., Microfabrication technology for polycaprolactone, a biodegradable polymer (2000) J Micromech Microeng, 10, pp. 80-84Murillo, M., Gamazo, C., Goñi, M.M., Irache, J.M., Blanco-Prieto, M.J., Development of microparticles prepared by spray-drying as a vaccine delivery system against brucellosis (2002) Inter J Pharm, 242, pp. 341-34