Intelligent hydrogels for the oral delivery of chemotherapeutics.
A novel approach toward improvements of oral chemotherapeutic formulations has evolved, which combines solubilisation (molecular dispersion) of the hydrophobic anticancer drugs in micelles attached to large macromolecules or microparticles. The large size of the macromolecules or microgels prevents the gel components from being transported into the systemic circulation. The discussed gels comprise copolymers of poly(acrylic acid) (PAA) and Pluronic surfactants, linked via C-C bonds. The Pluronic-PAA copolymers are non-irritating when administered orally. The micelles formed in the Pluronic-PAA solutions and in crosslinked microgels can be loaded with chemotherapeutic drugs and then released in contact with the intestine. The microgels are collapsed at the acidic pH of the stomach and expand, thus releasing the loaded drugs at the pH of the lower gastrointestinal tract. Yet the microgels are mucoadhesive and enable longer retention time and prolonged release in the colon. Ease of preparation and formulation of the drugs with the Pluronic-PAA polymers and gels may enable the wider use of oral chemotherapy, resulting in a better patient compliance and improved quality of life of the patients.
Bromberg
Lev
L
Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA 02139, USA. cpbrolev@mit.edu
D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008823:Micelles; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
D000180:Acrylic Resins; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D008823:Micelles; D013501:Surface-Active Agents; D020442:Poloxamer; C006903:carbopol 940; D004317:Doxorubicin