Controlled Release of Ionic Drugs from Complex Micelles with Charged Channels

• Published in: Biomacromolecules Vol. 13; no. 5; pp. 1307 - 1314
• Main Authors: Liu, Xiaojun, Ma, Rujiang, Shen, Junyang, Xu, Yanshuang, An, Yingli, Shi, Linqi
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14.05.2012
• Subjects: Applied sciences; Biological and medical sciences; Diffusion; Doxorubicin - chemistry; Exact sciences and technology; General pharmacology; Hydrogen-Ion Concentration; Ibuprofen - chemistry; Ions - chemistry; Medical sciences; Micelles; Molecular Structure; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polymers - chemical synthesis; Polymers - chemistry; Properties and characterization; Solubility; Solution and gel properties; Antineoplastic agent; Ring opening polymerization; Hydrodynamic radius; Mixed micelle; Radius of gyration; Drug carrier; Doxorubicin; Nanoencapsulation; Caprolactone copolymer; Ibuprofen; pH; Acid copolymer; Release; Amphiphilic polymer; Control release polymer; Aspartic derivative copolymer; Ethylene oxide copolymer; Experimental study; Non steroidal antiinflammatory agent; Polyelectrolyte; Preparation; Diblock copolymer; Kinetics; Aqueous solution; Micellar solution
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm2018382

Oral administration of ionic drugs generally encounters with significant fluctuation in plasma concentration due to the large variation of pH value in the gastrointestinal tract and the pH-dependent solubility of ionic drugs. Polymeric complex micelles with charged channels on the surface provided us with an effective way to reduce the difference in the drug release rate upon change in pH value. The complex micelles were prepared by self-assembly of PCL-b-PAsp and PCL-b-PNIPAM in water at room temperature with PCL as the core and PAsp/PNIPAM as the mixed shell. With an increase in temperature, PNIPAM collapsed and enclosed the PCL core, while PAsp penetrated through the PNIPAM shell, leading to the formation of negatively charged PAsp channels on the micelle surface. Release behavior of ionic drugs from the complex micelles was remarkably different from that of usual core–shell micelles where diffusion and solubility of drugs played a key role. Specifically, it was mainly dependent on the conformation of the PAsp chains and the electrostatic interaction between PAsp and drugs, which could partially counteract the influence of pH-dependent diffusion and solubility of drugs. As a result, the variation of drug release rate with pH value was suppressed, which was favorable for acquiring relatively steady plasma drug concentration.