caa a22 4500 44531382X CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-011-0375-z doi (NATIONALLICENCE)springer-10.1007/s11095-011-0375-z Development and In Vitro-In Vivo Evaluation of Polymeric Implants for Continuous Systemic Delivery of Curcumin [Elektronische Daten] [Shyam Bansal, Manicka Vadhanam, Ramesh Gupta] ABSTRACT: 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 ± 20ng/g in the liver after fourdays of implantation and was almost constant (8-15ng/g) for up to 35days. 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. Springer Science+Business Media, LLC, 2011 bioavailability nationallicence chemoprevention nationallicence controlled release nationallicence curcumin nationallicence implants nationallicence ACN : acetonitrile nationallicence BCS : bovine calf serum nationallicence CYP 1A1 : cytochrome P450 1A1 nationallicence DCM : dichloromethane nationallicence DSC : differential scanning calorimetry nationallicence ECF : extracellular fluid nationallicence FT-IR : Fourier transform infrared spectroscopy nationallicence GSTM : glutathione S-transferase (μ) nationallicence HPCD : 2-hydroxyl propyl β-cyclodextrin nationallicence PBS : phosphate-buffered-saline nationallicence PCL : poly (ε-caprolactone) nationallicence PEG 8K : polyethylene glycol (molecular weight 8,000) nationallicence PXRD : powder X-ray diffraction nationallicence SEM : scanning electron microscopy nationallicence Bansal Shyam Department of Pharmacology and Toxicology, University of Louisville, 40202, Louisville, Kentucky, USA aut Vadhanam Manicka James Graham Brown Cancer Center, University of Louisville, Delia Baxter II, Room 304E 580 Preston Street, 40202, Louisville, Kentucky, USA aut Gupta Ramesh Department of Pharmacology and Toxicology, University of Louisville, 40202, Louisville, Kentucky, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1121-1130 0724-8741 28:5<1121 2011 28 11095 https://doi.org/10.1007/s11095-011-0375-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0375-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bansal Shyam Department of Pharmacology and Toxicology, University of Louisville, 40202, Louisville, Kentucky, USA aut NATIONALLICENCE 700 1- Vadhanam Manicka James Graham Brown Cancer Center, University of Louisville, Delia Baxter II, Room 304E 580 Preston Street, 40202, Louisville, Kentucky, USA aut NATIONALLICENCE 700 1- Gupta Ramesh Department of Pharmacology and Toxicology, University of Louisville, 40202, Louisville, Kentucky, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1121-1130 0724-8741 28:5<1121 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer