DUAL ANTICANCER DRUG LOADED METHOXY POLY (ETHYLENE GLYCOL)-POLY (ε-CAPROLACTONE) BLOCK COPOLYMERIC MICELLES AS NOVEL DRUG CARRIERS

  • Anjan Kumar Mohanty Department of Pharmacy, Annamalai University, Tamilnadu, India 608002
  • Guru Prasad Mohanta Department of Pharmacy, Annamalai University, Tamilnadu, India 608002

Abstract

Objective: Curcumine (CUR) and rapamycin (RAPA) are two potent hydrophobic anticancer drugs. The clinical and preclinical applications of anticancer formulations are limited due to use of toxic excipients and poor bioavailability. In the present study, an approach has been made to develop CUR and RAPA loaded MePEG/PCL di-block copolymeric micelles keeping in the view to make excipient free formulation with slow release of drugs.

Methods: The CUR and RAPA loaded MePEG/PCL di-block copolymeric micelles were prepared. Physico-chemical characters like size, surface charge and encapsulation efficiency were measured. The in vitro release studies was carried out in pH 7.4 to evaluate the sustained release properties of micelles.

Results: MePEG/PCL di-block copolymeric micelles were efficiently encapsulate both the drugs, i. e. CUR (~ 64 %) and RAPA (~ 94 %) in the core and have loading capacity of ~ 12 % (CUR) and ~ 29 % (RAPA). The zetasizer measurement shows that particles have size range 128 nm to 176 nm with a negative zeta potential. SEM and AFM studies reveled that micelles have smooth exterior surface. The XRD and DSC studies explain that the drugs are uniformly distributed in the polymer matrix. The dual drug loaded micelles have sustained in vitro drug release activity as estimated in phosphate buffer (pH 7.4).

Conclusion: These MePEG/PCL di-block copolymeric micelles are capable of carrying both the hydrophobic anticancer drugs and the encouraging results suggest further studies to evaluate the bioavailability parameters as well as suitability of the formulation.

Keywords: Curcumin, Rapamycin, Poly (ethylene glycol)/ ε- caprolactone block copolymers, Micelles.

Downloads

Download data is not yet available.

Author Biography

Anjan Kumar Mohanty, Department of Pharmacy, Annamalai University, Tamilnadu, India 608002

Department of Pharmacy

Annamalai University

References

Aliabadi HM, Shahin M, Brocks DR, Lavasanifar A. Disposition of drugs in block copolymer micelle delivery systems: from discovery to recovery. Clin Pharmacokinet 2008;47:619-34.
2. Kwon GS. Editorial for theme section on polymeric micelles for drug delivery. Pharm Res 2008;25:2053-5.
3. Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems. J Control Release 2001;73:137-72.
4. Vakil R, Kwon GS. Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media. Langmuir 2006;22:9723-9.
5. Ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles: implications for cancer chemotherapy. Clin Pharmacokinet 2003;42:665-85.
6. Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, et al. Hypersensitivity reactions from taxol. J Clin Oncol 1990;8:1263-8.
7. Lorenz W, Reimann HJ, Schmal A, Dormann P, Schwarz B, Neugebauer E, et al. Histamine release in dogs by Cremophor E1 and its derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 1977;7:63-7.
8. Dye D, Watkins J. Suspected anaphylactic reaction to Cremophor EL. Br Med J 1980;280:1353.
9. Li Y, Jin M, Shao S, Huang W, Yang F, Chen W, et al. Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model. BMC Cancer 2014;14:329.
10. Mohanty AK, Dilnawaz F, Mohanty C, Sahoo SK. Etoposide-loaded biodegradable amphiphilic methoxy (poly ethylene glycol) and poly (epsilon caprolactone) copolymeric micelles as drug delivery vehicle for cancer therapy. Drug Deliv 2010;17:330-42.
11. Mohanty C, Acharya S, Mohanty AK, Dilnawaz F, Sahoo SK. Curcumin-encapsulated MePEG/PCL diblock copolymeric micelles: a novel controlled delivery vehicle for cancer therapy. Nanomedicine (Lond) 2010;5:433-49.
12. Kim SY, Lee YM. Taxol-loaded block copolymer nanospheres composed of methoxy poly(ethylene glycol) and poly(epsilon-caprolactone) as novel anticancer drug carriers. Biomaterials 2001;22:1697-704.
13. Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, et al. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res 2004;10:3708-16.
14. Aryal S, Hu CM, Zhang L. Combinatorial drug conjugation enables nanoparticle dual-drug delivery. Small 2010;6:1442-8.
15. Hu C-MJ, Aryal S, Zhang L. Nanoparticle-assisted combination therapies for effective cancer treatment. Therapeutic Delivery 2010;1:323-34.
16. Shin HC, Alani AW, Rao DA, Rockich NC, Kwon GS. Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs. J Control Release 2009;140:294-300.
17. Feng SS, Mu L, Win KY, Huang G. Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. Curr Med Chem 2004;11:413-24.
18. Dorofeev GA, Streletskii AN, Povstugar IV, Protasov AV, Elsukov EP. Determination of nanoparticle sizes by X-ray diffraction. Colloid J 2012;74:675-85.
19. Sehgal SN, Baker H, Vézina C. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J of Antibio (Tokyo) 1975;28:727-32.
20. Shin IG, Kim SY, Lee YM, Cho CS, Sung YK. Methoxy poly(ethylene glycol)/epsilon-caprolactone amphiphilic block copolymeric micelle containing indomethacin. I. Preparation and characterization. J Control Release 1998;51:1-11.
21. Kreuter J, Gelperina S. Use of nanoparticles for cerebral cancer. Tumori 2008;94:271-7.
22. Yao B, He QM, Tian L, Xiao F, Jiang Y, Zhang R, et al. Enhanced antitumor effect of the combination of tumstatin gene therapy and gemcitabine in murine models. Hum Gene Ther 2005;16:1075-86.
23. Parhi P, Mohanty C, Sahoo SK. Nanotechnology based combinational drug delivery: an emerging approach for cancer therapy. Drug Discovery Today 2012;17:1044-52.
24. Shin HC, Alani AW, Cho H, Bae Y, Kolesar JM, Kwon GS. A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs. Mol Pharm 2011;8:1257-65.
25. Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today 2003;8:1112-20.
26. Yokoyama T, Tam J, Kuroda S, Scott AW, Aaron J, Larson T, et al. EGFR-targeted hybrid plasmonic magnetic nanoparticles synergistically induce autophagy and apoptosis in non-small cell lung cancer cells. PLoS One 2011;6:e25507.
27. Marathe SA, Ray S, Chakravortty D. Curcumin increases the pathogenicity of Salmonella enterica serovar Typhimurium in murine model. PLoS One 2010;5:e11511.
Statistics
347 Views | 577 Downloads
How to Cite
Mohanty, A. K., and G. P. Mohanta. “DUAL ANTICANCER DRUG LOADED METHOXY POLY (ETHYLENE GLYCOL)-POLY (ε-CAPROLACTONE) BLOCK COPOLYMERIC MICELLES AS NOVEL DRUG CARRIERS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 6, no. 9, 1, pp. 328-32, https://innovareacademics.in/journals/index.php/ijpps/article/view/2341.
Section
Original Article(s)