CAMPTOTHECIN LOADED POLY (METHACYCLIC ACID-CO-METHYL-METHYACRYLATE) NANOPARTICLES: FABRICATION, CHARACTERIZATION AND CYTOTOXICITY STUDIES
Keywords:
Camptothecin, Cytotoxicity, Drug release, MTT assay, Nanoparticles, Particle sizeAbstract
Objectives: The present investigation was aimed to fabricate Camptothecin loaded Poly (Methacyclic acid-co-methyl-methyacrylate) nanoparticles to characterize the prepared nanoparticles and to evaluate the cytotoxicity of prepared Camptothecin.
Methods: Camptothecin loaded polymeric nanoparticles were prepared by nanoprecipitation method by sonication approach. The prepared nanoparticles were evaluated for particle size, particle size uniformity, surface area, zeta potential, surface morphology, encapsulation efficacy, drug loading and in-vitro drug release. To evaluate the potential anticancer efficacy of nanoparticulate system, in-vitro cytotoxicity studies on human colon cancer cell line (HT-29) were carried out using MTT assay.
Results: Camptothecin loaded polymeric nanoparticles were successfully prepared by nano precipitation method using sonication approach. Nanoparticles prepared using sonication method were with an average particle size 100 to 200 nm, particle size uniformity found to be<0.3 and zeta potential>20mV. Prepared Camptothecin loaded polymeric nanoparticles were spherical in shape and showed excellent encapsulation efficiency and drug loading. The release profile was found to be pH dependent. It was observed that polymer coated Camptothecin nanoparticles gave no release in simulated gastric fluid, negligible release in simulated intestinal fluid and maximum release in colonic environment. The drug release followed Hixson Crowell cube root law model. Prepared Camptothecin loaded polymeric nano formulations displayed enhanced cytotoxicity against HT-29 cells in comparison with pure Camptothecin.
Conclusion: In summary, Camptothecin loaded Poly (Methacyclic acid-co-methyl-methyacrylate) nanoparticles may be considered as an attractive and promising formulation. Thus, the results indicate the potential for in-vivo studies for the developed pH sensitive nanoparticles of Camptothecin to establish their clinical application.
Â
Downloads
References
Dandekar Prajakta, Jain Ratnesh, Kumar Chandan, Subramanian Suresh, Samuel Grace, Venkatesh Meera, et al. Curcumin loaded pH-sensitive nanoparticles for the treatment of colon cancer. J Biomed Nanotechnol 2009;5:445-55.
Giftson Senapathy J, Jayanthi S, Viswanathan P, Umadevi P, Nalini N. Effect of gallic acid on xenobiotic metabolizing enzymes in 1,2-dimethyl hydrazine induced colon carcinogenesis in wistar rats-a chemopreventive approach. Food Chem Toxicol 2011;49:887-92.
Leonard Saltz. The chemotherapy-naive patient with metastatic colorectal cancer. Commu Oncol 2007;4:5-7.
Madhavi M, Madhavi K, Jithan AV. Preparation and in vitro/in vivo characterization of curcumin microspheres intended to treat colon cancer. J Pharm Bioall Sci 2012;4:164-71.
Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery systems. J Pharm Pharm Sci 2003;6:33-66.
Sarasija S, Hota A. Colonspecific drug delivery systems. Indian J Pharm Sci 2000;62:1-8.
Kinget R, Kalala W, Vervoort L, Van den Mooter G. Colonic drug targeting. J Drug Target 1998;6:129-49.
Manikandan Mahalingam, Kannan Krishnamoorthy. Selection of a suitable method for the preparation of polymeric nanoparticles: multi-criteria decision making approach. Adv Pharm Bull 2015;5:57-67.
Vargas A, Pegaz B, Debefve E, Konan-Kouakou Y, Lange N, Ballini JP. Improved photodynamic activity of porphyrin loaded into nanoparticles: an in vivo evaluation using chick embryos. Int J Pharm 2004;286:131-45.
Cheng-Liang Peng, Ping-Shan Lai, Feng-Huei Lin, Steven Yueh-Hsiu Wu, Ming-Jium Shieh. Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles. Biomaterials 2009;30:3614-25.
Anna Valeria Vergoni, Giovanni Tosi, Raffaella Tacchi, Maria Angela Vandelli, Alfio Bertolini, Luca Costantino. Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution. Nanomedicine 2009;5:369-77.
Manikandan M, Kannan K, Manavalan R. Compatibility studies of camptothecin with various pharmaceutical excipients used in the development of nanoparticle formulation. Int J Pharm Pharm Sci 2013;5:315-21.
Erkki Ruoslahti, Sangeeta N Bhatia, Michael J Sailor. Targeting of drugs and nanoparticles to tumors. J Cell Biol 2010;188:759-68.
Asghar LF, Chandran S. Multiparticulate formulation approach to colon specific drug delivery: current perspectives. J Pharm Pharm Sci 2006;9:327-38.
Fessi H, Puisieux F, Devissaguet J, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 1989;55:R1-4.
Moorthi C, Kathiresan K. Fabrication of dual drug loaded polymeric nanosuspension: Incorporating analytical hierarchy process and data envelopment analysis in the selection of a suitable method. Int J Pharm Pharm Sci 2013;5:499-504.
Rao JP, Geckeler KE. Polymer nanoparticles: preparation techniques and sizecontrol parameters. Prog Polym Sci 2011;36:887-913.
Champion JA, Katare YK, Mitragotri S. Particle shape: a new design parameter for micro-and nanoscale drug delivery carriers. J Controlled Release 2007;121:3-9.
Moorthi C, Kiran Krishnan, Manavalan R, Kathiresan K. Preparation and characterization of curcumin-piperine dual drug loaded nanoparticles. Asian Pac J Trop Biomed 2012;841-8.
Rajan K Verma, Sanjay Garg. Selection of excipients for extended release formulations of glipizide through drug-excipient compatibility testing. J Pharm Biomed Anal 2005;38:633-44.
Nihar Ranjan Pani, Lila Kanta Nath, Sujata Acharya. Compatibility studies of nateglinide with excipients in immediate release tablets. Acta Pharm 2011;61:237-47.
Choudhury PK, Murthy PN, Tripathy NK, Panigrahi R, Behera S. Investigation of drug polymer compatibility: Formulation and characterization of metronidazole microspheres for colonic delivery. Web Med Central 2012;3:1-20.
Shahe Mahammad S, Madhusudhana Chetty, Ramana Murthy KV. Preformulation studies of quetiapine fumarate. J Pharm Res 2012;5:672-7.
Karin Liltorp, Trine Gorm Larsenb, Birgitte Willumsenb, Rene Holma. Solid state compatibility studies with tablet excipients using non thermal methods. J Pharm Biomed Anal 2011;55:424-8.
Seema Badhana, Navneet Garud, Akanksha Garud. Colon specific drug delivery of mesalamine using eudragit S100-coated chitosan microspheres for the treatment of ulcerative colitis. Int Curr Pharm J 2013;2:42-8.
Ahmed Abd El-Bary, Ahmed A Aboelwafa, Ibrahim M Al Sharabi. Influence of some formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release Mesalamine microspheres. AAPS Pharm Sci Tech 2012;13:75-84.
Francis D, Rita L. Rapid colorometric assay for cell growth and survival modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986;89:271-7.
Pavan Kumar Bellamakondi, Ashok Godavarthi, Mohammed Ibrahim, Seetaram Kulkarni, Ramchandra Naik M, Maradam Sunitha. In vitro cytotoxicity of caralluma species by MTT and Trypan blue dye exclusion. Asian J Pharm Clin Res 2014;7:17-9.
Chandran S, Sanjay KS, Ali Asghar LF. Microspheres with pH modulated release: design and characterization of formulation variables for colonic delivery. J Microencapsul 2009;26:420-31.
Sinha VR, Kumria R. Coating polymers for colon specific drug delivery: a comparative in vitro evaluation. Acta Pharm 2003;53:41-7.