TY - JOUR
T1 - Development and in vitro-in vivo evaluation of polymeric implants for continuous systemic delivery of curcumin
AU - Bansal, Shyam S.
AU - Vadhanam, Manicka V.
AU - Gupta, Ramesh C.
N1 - Funding Information:
This research work was supported from USPHS grants CA-118114, CA-125152, CA-90892, and from Agnes Brown Duggan Endowment. R.C.G. is Agnes Brown Duggan Chair in Oncological Research. Dr. Hina Kausar is acknowledged for her assistance in the western blot studies.
PY - 2011/5
Y1 - 2011/5
N2 - Purpose: The introduction of curcumin into clinics is hindered by its low water solubility and poor bioavailability. To overcome these limitations, we developed curcumin implants using poly (ε-caprolactone) as the polymeric matrix. Methods: Implants were prepared by melt-extrusion method; in vitro drug release was optimized for effects of polymer composition, drug load, surface area and water-soluble additives. Implants were also tested under in vivo conditions for cumulative curcumin release, and liver concentration was correlated with its efficacy to modulate selected xenobiotic-metabolizing enzymes (CYP1A1 and GSTM). Results: Drug release from implants followed biphasic release pattern with Higuchi kinetics and was proportional to the surface area of implants. Drug release increased proportionately from 2 to 10% (w/w) drug load, and incorporation of 10% (w/w) of water-soluble additives (F-68, PEG 8000 and cyclodextrin) did not significantly alter the drug release. In vivo drug release was found to be ×1.8 times higher than in vitro release. Curcumin was detected at 60∈±∈20 ng/g in the liver after four days of implantation and was almost constant (8-15 ng/g) for up to 35 days. This time-dependent drop in curcumin level was found to be due to induction of CYP1A1 and GSTM (μ) enzymes which led to increased metabolism of curcumin. Conclusion: Our data showed that these implants were able to release curcumin for long duration and to modulate liver phase I and phase II enzymes, demonstrating curcumin's biological efficacy delivered via this delivery system.
AB - Purpose: The introduction of curcumin into clinics is hindered by its low water solubility and poor bioavailability. To overcome these limitations, we developed curcumin implants using poly (ε-caprolactone) as the polymeric matrix. Methods: Implants were prepared by melt-extrusion method; in vitro drug release was optimized for effects of polymer composition, drug load, surface area and water-soluble additives. Implants were also tested under in vivo conditions for cumulative curcumin release, and liver concentration was correlated with its efficacy to modulate selected xenobiotic-metabolizing enzymes (CYP1A1 and GSTM). Results: Drug release from implants followed biphasic release pattern with Higuchi kinetics and was proportional to the surface area of implants. Drug release increased proportionately from 2 to 10% (w/w) drug load, and incorporation of 10% (w/w) of water-soluble additives (F-68, PEG 8000 and cyclodextrin) did not significantly alter the drug release. In vivo drug release was found to be ×1.8 times higher than in vitro release. Curcumin was detected at 60∈±∈20 ng/g in the liver after four days of implantation and was almost constant (8-15 ng/g) for up to 35 days. This time-dependent drop in curcumin level was found to be due to induction of CYP1A1 and GSTM (μ) enzymes which led to increased metabolism of curcumin. Conclusion: Our data showed that these implants were able to release curcumin for long duration and to modulate liver phase I and phase II enzymes, demonstrating curcumin's biological efficacy delivered via this delivery system.
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U2 - 10.1007/s11095-011-0375-z
DO - 10.1007/s11095-011-0375-z
M3 - Article
C2 - 21311958
AN - SCOPUS:79955614848
SN - 0724-8741
VL - 28
SP - 1121
EP - 1130
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 5
ER -