Thermodynamic studies and loading of 7-ethyl-10-hydroxycamptothecin into mesoporous silica particles MCM-41 in strongly acidic solutions.
A major limitation of the clinical efficacy of the 7-ethyl-10-hydroxycamptothecin (SN38) therapy is its facile conversion of the active lactone form into a less active carboxylate species at physiological pH and limited aqueous solubility. The present manuscript embodies a detailed description of several physicochemical properties of SN38 and further details the thermodynamic basis for its poor aqueous solubility. The ionization and increased solubility of the drug in highly acidic media were subsequently employed to efficiently load the positively charged drug in its biologically active lactone form into mesoporous silica material of type MCM-41, achieving a maximum loading of 250 mg of SN38 per gram of silicate. It was also found that the equilibrium association constant K(A) varies with the extent of drug adsorption. At low and high drug load, corresponding to one SN38 molecule bound for every 70 and 13 -SiO(2)-, K(A) was determined to be 1253.5 and 127.39 M(-1), respectively.
Thakur
Rishi
R
Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy & Health Sciences, Long Island University, Brooklyn, New York 11201, USA.
Sivakumar
Balasubramanian
B
Savva
Michalakis
M
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D000077146:Irinotecan; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D012996:Solutions / Q000737:chemistry*; D013816:Thermodynamics
D000972:Antineoplastic Agents, Phytogenic; C509968:MCM-41; D012996:Solutions; D012822:Silicon Dioxide; D000077146:Irinotecan; D002166:Camptothecin