Abstract
This study reports scale-up and shelf-stability of curcumin encapsulated poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles. The curcumin encapsulated PLGA nanoparticles were prepared by emulsification solvent evaporation/diffusion, and large quantities were made by varying the homogenisation time (5, 15 and 30 min). The particle size decreased as the homogenisation duration increased from 5 to 30 min, and the particles were spherical as confirmed by atomic force microscopy. For the large-scale preparations, the mean particles size was found to be 288.7 ± 3.4 (polydispersity index 0.15 ± 0.01) with curcumin entrapment 52.5 ± 4.3 %, which were comparable to the lab-scale preparations. The curcumin encapsulated nanoparticles were freeze-dried using sucrose (5 %, w/v) as a cryoprotectant. The freeze-dried nanoparticles were subjected to 6-month stability study as per the International Conference on Harmonisation guideline at room temperature and refrigerated storage conditions. Intermediate sampling was done (monthly), and the nanoparticles were thoroughly characterised for particle size, entrapment efficiency, surface morphology and crystallinity, which were compared to fresh preparations. The curcumin encapsulated PLGA nanoparticles were found to be stable at refrigerated as well as room temperature storage test conditions indicated by their particle characteristics. X-ray diffraction results confirm amorphous nature of curcumin on nano-encapsulation that stays intact after freeze drying and 6-month stability testing. Together these data offer possibility of producing large quantities of polymer nanoparticles that are suitable for room as well as refrigerated storage conditions opening up possibilities to conduct repeated dosings in a chronic setting or regulatory toxicology studies of such nanomedicines.
Similar content being viewed by others
References
Kreuter J. Nanoparticles—a historical perspective. Int J Pharm. 2007;331:1–10.
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.
LaVan DA, McGuire T, Langer R. Small-scale systems for in vivo drug delivery. Nat Biotechnol. 2003;21:1184–91.
Devadasu VR, Bhardwaj V, Kumar MNVR. Can controversial nanotechnology promise drug delivery? Chem Rev. 2013. doi:10.1021/cr300047q.
Grama CN, Ankola DD, Kumar MNVR. Poly(lactide-co-glycolide) nanoparticles for peroral delivery of bioactives. Curr Opin Colloid Interface Sci. 2011;16:238–45.
Holzera M, Vogel V, Mäntele W, Schwartz D, Haased W, Langer K. Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage. Eur J Pharm Biopharm. 2009;72:428–37.
Shaikh J, Ankola DD, Beniwal V, Singh D, Kumar MNVR. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci. 2009;37:223–30.
Kumar MNVR. Can efficient delivery systems leverage benefits of antioxidants leading to potential medicines? Drug Discov Today. 2012;17:407–8.
Devadasu VR, Ankola DD, Bhardwaj V, Sahana DK, Kumar MNVR. Role of antioxidants in prophylaxis and therapy: a pharmaceutical perspective. J Control Release. 2006;113:189–207.
Burgos-Moron E, Calderon-Montano JM, Salvador J, Robles A, Lopez-Lazaro ML. The dark side of curcumin. Int J Cancer. 2010;126:1771–5.
Devadasu VR, Wadsworth RM, Kumar MNVR. Tissue localization of nanoparticles is altered due to hypoxia resulting in poor efficacy of curcumin nanoparticles in pulmonary hypertension. Eur J Pharm Biopharm. 2012;80:578–84.
Devadasu VR, Wadsworth RM, Kumar MNVR. Protective effects of nanoparticulate coenzyme Q10 and curcumin on free radical damage in streptozotocin-induced diabetic rats: a possible remedy to diabetic complications. Drug Deliv Transl Res. 2011;1:1448–55.
Muthenna P, Suryanarayana P, Gunda SK, Petrash JM, Reddy GB. Inhibition of aldose reductase by dietary antioxidant curcumin: mechanism of inhibition, specificity and significance. FEBS Lett. 2009;583:3637–42.
Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res. 2007;13:3423–30.
http://www.clinicaltrials.gov/ct2/results?term=curcumin&Search=Search
Kundu P, Mohanty C, Sahoo SK. Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy. Acta Biomater. 2012;8:2670–87.
Chun YS, Bisht S, Chenna V, Pramanik D, Yoshida T, Hong SM, et al. Intraductal administration of a polymeric nanoparticle formulation of curcumin (NanoCurc) significantly attenuates incidence of mammary tumors in a rodent chemical carcinogenesis model: implications for breast cancer chemoprevention in at-risk populations. Carcinogenesis. 2012;33:2242–9.
Ranjan AP, Mukerjee A, Helson L, Vishwanatha JK. Scale up, optimization and stability analysis of curcumin C3 complex-loaded nanoparticles for cancer therapy. J Nanobiotechnol. 2012;10:38–56.
Acknowledgments
The authors are thankful to the Cancer Research UK Formulation Unit, SIPBS for permitting the use of ICH stability test chambers. Partial financial support by Cunningham Trust in the form of research grant (ACC/KWF/CT10/01) to MNVRK is acknowledged. C. N. Grama is grateful to University of Strathclyde for partial financial support towards her PhD studies. The authors acknowledge the instrument support from the Engineering and Physical Sciences Research Council (grant EP/E036244/1). Thanks are due to Vishal Raval for helping with XRD analysis.
Conflict of interest
Charitra N. Grama, Vinod P. Venkatpurwar, Dimitrios A. Lamprou and M. N.V. Ravi Kumar declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Grama, C.N., Venkatpurwar, V.P., Lamprou, D.A. et al. Towards scale-up and regulatory shelf-stability testing of curcumin encapsulated polyester nanoparticles. Drug Deliv. and Transl. Res. 3, 286–293 (2013). https://doi.org/10.1007/s13346-013-0150-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13346-013-0150-2