PURPOSE: A novel polymer micelle was prepared with a high drug loading, good stability, high tolerance and better anti-tumor effect. METHODS: TM-2 was encapsulated in poly-block-poly (D, L-lactic acid) self-assembled micelles by the thin-film hydration method. From the critical micelle concentrations of the copolymers, particle size, drug loading and encapsulation efficiency of drug-loading micelles, the appropriate polymer material could be assessed. Comparisons between TM-2 solution and TM-2 micelles were done to evaluate the pharmacokinetics and toxicity in rats, compared with Taxol to evaluate the anti-tumor effect in mice. RESULTS: The optimized TM-2 micelles achieved a high drug loading (~20%) with the polymer material of PEG2k-PLA2.5k, with a particle size of 30 nm and no significant change in particle size after lyophilization. The result of pharmacokinetic experiment displayed that the half-life in vivo was obviously prolonged. The maximum tolerated dose of TM-2 micelles was approximately 25 mg/kg in rats, and the relative tumor growth rate of Taxol (15 mg/kg), TM-2 (10 mg/kg), TM-2 (15 mg/kg) and TM-2 (40 mg/kg) in mice were 49.35%, 49.14%, 36.44 and 9.98% respectively. CONCLUSIONS: TM-2 micelles with high drug loading increased drug solubility, improved tolerance, antitumor effects and reduced toxicity.
PURPOSE: A novel polymer micelle was prepared with a high drug loading, good stability, high tolerance and better anti-tumor effect. METHODS:TM-2 was encapsulated in poly-block-poly (D, L-lactic acid) self-assembled micelles by the thin-film hydration method. From the critical micelle concentrations of the copolymers, particle size, drug loading and encapsulation efficiency of drug-loading micelles, the appropriate polymer material could be assessed. Comparisons between TM-2 solution and TM-2 micelles were done to evaluate the pharmacokinetics and toxicity in rats, compared with Taxol to evaluate the anti-tumor effect in mice. RESULTS: The optimized TM-2 micelles achieved a high drug loading (~20%) with the polymer material of PEG2k-PLA2.5k, with a particle size of 30 nm and no significant change in particle size after lyophilization. The result of pharmacokinetic experiment displayed that the half-life in vivo was obviously prolonged. The maximum tolerated dose of TM-2 micelles was approximately 25 mg/kg in rats, and the relative tumor growth rate of Taxol (15 mg/kg), TM-2 (10 mg/kg), TM-2 (15 mg/kg) and TM-2 (40 mg/kg) in mice were 49.35%, 49.14%, 36.44 and 9.98% respectively. CONCLUSIONS:TM-2 micelles with high drug loading increased drug solubility, improved tolerance, antitumor effects and reduced toxicity.
Entities:
Keywords:
anti-tumor effect; high drug loading; polymer micelles; tm-2; toxicity
Authors: Nuhad K Ibrahim; Neil Desai; Sewa Legha; Patrick Soon-Shiong; Richard L Theriault; Edgardo Rivera; Bita Esmaeli; Sigrid E Ring; Agop Bedikian; Gabriel N Hortobagyi; Julie A Ellerhorst Journal: Clin Cancer Res Date: 2002-05 Impact factor: 12.531
Authors: Jeffrey Hrkach; Daniel Von Hoff; Mir Mukkaram Ali; Elizaveta Andrianova; Jason Auer; Tarikh Campbell; David De Witt; Michael Figa; Maria Figueiredo; Allen Horhota; Susan Low; Kevin McDonnell; Erick Peeke; Beadle Retnarajan; Abhimanyu Sabnis; Edward Schnipper; Jeffrey J Song; Young Ho Song; Jason Summa; Douglas Tompsett; Greg Troiano; Tina Van Geen Hoven; Jim Wright; Patricia LoRusso; Philip W Kantoff; Neil H Bander; Christopher Sweeney; Omid C Farokhzad; Robert Langer; Stephen Zale Journal: Sci Transl Med Date: 2012-04-04 Impact factor: 17.956
Authors: Daniel D Von Hoff; Monica M Mita; Ramesh K Ramanathan; Glen J Weiss; Alain C Mita; Patricia M LoRusso; Howard A Burris; Lowell L Hart; Susan C Low; Donald M Parsons; Stephen E Zale; Jason M Summa; Hagop Youssoufian; Jasgit C Sachdev Journal: Clin Cancer Res Date: 2016-02-04 Impact factor: 12.531
Authors: Zhijian He; Xiaomeng Wan; Anita Schulz; Herdis Bludau; Marina A Dobrovolskaia; Stephan T Stern; Stephanie A Montgomery; Hong Yuan; Zibo Li; Daria Alakhova; Marina Sokolsky; David B Darr; Charles M Perou; Rainer Jordan; Robert Luxenhofer; Alexander V Kabanov Journal: Biomaterials Date: 2016-06-04 Impact factor: 12.479
Authors: Darya A Stepanova; Vladislava A Pigareva; Anna K Berkovich; Anastasia V Bolshakova; Vasiliy V Spiridonov; Irina D Grozdova; Andrey V Sybachin Journal: Polymers (Basel) Date: 2022-09-25 Impact factor: 4.967