TY - JOUR
T1 - Curcumin implants for continuous systemic delivery
T2 - Safety and biocompatibility
AU - Bansal, Shyam S.
AU - Kausar, Hina
AU - Aqil, Farrukh
AU - Jeyabalan, Jeyaprakash
AU - Vadhanam, Manicka V.
AU - Gupta, Ramesh C.
AU - Ravoori, Srivani
N1 - Funding Information:
Authors are thankful to Sabinsa Corporation for generously providing us with GMP grade curcumin (C3 complex). This research work was supported from USPHS grants CA-118114 CA-125152 and CA-90892 and from Agnes Brown Duggan Endowment. R.C.G. is Agnes Brown Duggan Chair in Oncological Research.
PY - 2011/8
Y1 - 2011/8
N2 - Curcumin, an anti-oxidant, anti-inflammatory, and anti-neoplastic agent, exhibited limited oral efficacy due to its poor bioavailability. To overcome this limitation, polymeric implants for continuous systemic delivery of curcumin were developed and tested for their safety and biocompatibility. Two 2-cm polycaprolactone implants containing polyethylene glycol and 20% (w/w) curcumin were grafted subcutaneously at the back of the Augustus Copenhagen Irish rats. Rats were euthanized and blood was analyzed for various hematological parameters; biochemical markers of liver/kidney function and local tissues were analyzed for local inflammatory reactions. Curcumin implants exhibited biphasic release kinetics with ~3. 6 + 0. 8, 5. 8 ± 1. 1, 13. 1 ± 2. 1, 21. 8 ± 0. 3, 38. 1 ± 0. 6, and 47. 2 ± 1. 6 mg cumulative curcumin being released from both the implants after 1, 4, 12, 25, and 90 days. No significant differences in various hematological parameters (like white blood cells, red blood cells, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin), liver enzymes (like aspartate transaminase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, amylase, or lipase), or biochemical parameters of kidney function (like blood urea nitrogen, creatinine, Ca 2+, Na +, and Cl - levels) were observed at any of these time points. However, a significant increase in serum phosphorus levels was observed at all the time points in sham implants as well as in curcumin diet and implant groups. Local implantation site showed foreign body granulomatous reaction with influx of histiocytes and occasional multi-nucleated giant cells with sham implants and was minimal around the curcumin implants. These polymeric implants were found to have little or no systemic toxicity with an acute reaction at local site which was reduced significantly by curcumin implants.
AB - Curcumin, an anti-oxidant, anti-inflammatory, and anti-neoplastic agent, exhibited limited oral efficacy due to its poor bioavailability. To overcome this limitation, polymeric implants for continuous systemic delivery of curcumin were developed and tested for their safety and biocompatibility. Two 2-cm polycaprolactone implants containing polyethylene glycol and 20% (w/w) curcumin were grafted subcutaneously at the back of the Augustus Copenhagen Irish rats. Rats were euthanized and blood was analyzed for various hematological parameters; biochemical markers of liver/kidney function and local tissues were analyzed for local inflammatory reactions. Curcumin implants exhibited biphasic release kinetics with ~3. 6 + 0. 8, 5. 8 ± 1. 1, 13. 1 ± 2. 1, 21. 8 ± 0. 3, 38. 1 ± 0. 6, and 47. 2 ± 1. 6 mg cumulative curcumin being released from both the implants after 1, 4, 12, 25, and 90 days. No significant differences in various hematological parameters (like white blood cells, red blood cells, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin), liver enzymes (like aspartate transaminase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, amylase, or lipase), or biochemical parameters of kidney function (like blood urea nitrogen, creatinine, Ca 2+, Na +, and Cl - levels) were observed at any of these time points. However, a significant increase in serum phosphorus levels was observed at all the time points in sham implants as well as in curcumin diet and implant groups. Local implantation site showed foreign body granulomatous reaction with influx of histiocytes and occasional multi-nucleated giant cells with sham implants and was minimal around the curcumin implants. These polymeric implants were found to have little or no systemic toxicity with an acute reaction at local site which was reduced significantly by curcumin implants.
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U2 - 10.1007/s13346-011-0028-0
DO - 10.1007/s13346-011-0028-0
M3 - Article
AN - SCOPUS:84862994005
SN - 2190-393X
VL - 1
SP - 332
EP - 341
JO - Drug Delivery and Translational Research
JF - Drug Delivery and Translational Research
IS - 4
ER -