Controlled delivery system for norethindrone based on biodegradable poly-alpha,beta-(hydroxyalkyl)-DL-aspartamide.
The article describes the preparation of poly-(hydroxyalkyl)-DL-aspartamide (PHAA) by a (ring) opening reaction by hydroxyalkylamino; norethindrone (NET), as a model drug, was coupled to the polymers via hydroxyalkylamino spacers. PHAA and NETPHAA conjugates were characterized by FTIR, DSC, x-ray,(13)C NMR, and scanning electron microscopy and their structure were confirmed. The biocompatibility of PHAA was tested. The study showed that PHAA was a hydrophilic, nontoxic in vivo, nonantigenic material and had good biocompatibility as a drug carrier. The effect on drug release from the polymer of length of side chain, initial drug loading, and particle size of the polymer drug were investigated in tris-HCl buffer solution (pH 7.4, t = 37 degrees C). In vivo release in rabbits also was performed for 120 days. The experiment indicated that the concentration of NET in rabbits can be 1-2 microg/ml serum after 1 month; 10% of NET had been released from the polymer.
Tang
Guping
G
College of Pharmaceutical Science, Zhejiang University, Zhejiang, People's Republic of China. gp-tang@imre.org.sg
Zhu
Kangjie
K
Chen
Qiqi
Q
D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009640:Norethindrone / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011817:Rabbits
D003692:Delayed-Action Preparations; D010455:Peptides; D011108:Polymers; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D009640:Norethindrone