Novel polymeric micelles for drug delivery: Material characterization and formulation screening

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• 作者：Christine Janas^a ; Zouhair Mostaphaoui^a ; Ludwig Schmiederer^b ; Johann Bauer^b ; Matthias G. Wacker^c ; ^{matthias.wacker@ime.fraunhofer.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AAmBzA ; 4-acrylamido benzoic acid ; API ; active pharmaceutical ingredient ; ATRP ; atom transfer radical polymerization ; BP ; block copolymer ; BuMA ; butyl methacrylate ; BzMA ; benzyl methacrylate ; CMC ; critical micelle concentration ; cryo-TEM ; cryogenic transmission electron microscopy ; DiI ; 1&prime ; D-Dioctadecyl-3 ; 3 ; 3 ; 3&prime ; -tetramethylindocarbocyanine perchlorate ; DiO ; 3 ; 3&prime ; -Dioctadecyloxacarbocyanine perchlorate ; DLS ; dynamic light scattering ; FBS ; fetal bovine serum ; FRET ; Foerster resonan
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：25 July 2016
• 年：2016
• 卷：509
• 期：1-2
• 页码：197-207
• 全文大小：2382 K

文摘

A rising number of new chemical entities that exhibit only poor aqueous solubility are identified in drug discovery processes. Polymeric micelles composed of block copolymers (BP) facilitate the delivery of such lipophilic molecules in drug therapy. Consequently, a rational screening and selection procedure for novel BP was established. Further, the interplay of polymer structure, micelle formation and drug binding was studied. Therefore seven polymers (BP001 to BP007) were synthesized from different monomer compositions resulting in nanocarriers varying in surface decoration and lipophilicity. These polymers were characterized by H¹-NMR and SEC. The molecular weight was ranging between 13 and 37 kDa. The critical micelle concentration and micellar integrity in presence of human plasma were determined. Micelles were loaded with dexamethasone and characterized with regards to their size, morphology and surface charge. Polymeric micelles with a size of 49.21–236.37 nm were obtained. A half-life of 11 h was determined for five of the copolymers in presence of human plasma. Two nanocarrier formulations (BP006 and BP007) were exhibiting optimal micellar integrity in vitro and a modified release profile under biorelevant conditions. Strongest drug-polymer interaction was observed for nanocarrier compositions providing benzyl and carboxylic groups and were composed of BP006 and BP007.