ABSTRACT
The classically used nontargeted chemotherapeutic approach to pancreatic cancer has a dual drawback of suboptimal drug delivery at the target site and the systemic side effects produced by the unfettered exposure of the drug to healthy tissue. This study has the objective of developing novel poly(2-ethyl-2-oxazoline) (PETOX)-based long circulating liposomes loaded with gemcitabine and irinotecan for the treatment of pancreatic ductal adenocarcinoma, with a juxtaposition to PEGylated and uncoated liposomes. A PETOX-cholesteryl chloroformate lipopolymer conjugate (PETOX-ChC) with a carbonate linkage was prepared and characterized by 1H NMR, FTIR, and DSC. Liposomes were prepared using the thin film hydration technique followed by freeze-thaw and membrane extrusion methods. Liposome characterization includes particle size determination, zeta potential determination using a zetameter, and structural elucidation using 31P NMR and cryo-TEM. The PETOXylated liposomes showed a particle size of 180.1 ± 2.2 nm and a zeta potential of - 33.63 ± 1.23 mV. The liposomal combination therapy of gemcitabine and irinotecan was found to have an IC50 value 39 times lower in comparison to the drug combination in solution, while the PEGylated and PETOXylated liposomes showed IC50 values 1.6 times lower and 2 times lower than that of uncoated liposomes, respectively, against Mia PaCa II pancreatic cancer cell line. The PEGylated and PETOXylated liposomes showed 4.1 and 5.4 times slower macrophagial uptake in vitro in comparison to the uncoated liposomes respectively. The PEGylated liposomes showed 11% higher in vitro macrophagial uptake in comparison to PETOXylated liposomes.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Pancreatic Ductal/drug therapy , Deoxycytidine/analogs & derivatives , Irinotecan/administration & dosage , Liposomes , Pancreatic Neoplasms/drug therapy , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Deoxycytidine/administration & dosage , Drug Delivery Systems , Humans , Pancreatic Neoplasms/pathology , Particle Size , Polyethylene Glycols/chemistry , GemcitabineABSTRACT
The essential features of an appointments system are its structure, its practicability, the staff application, and the patient's accessibility and their education of its function, and how best to avail themselves of its benefits. A proposal for an appointments system in general practice is contained in a booklet produced by the Practice Management Committee of Council. The booklet also contains a report of the Medical Organization Committee of the Royal College of General Practitioners.
