Bencini Marco, Ranucci Elisabetta, Ferruti Paolo, Trotta Francesco, Donalisio Manuela, Cornaglia Maura, Lembo David, Cavalli Roberta
Dipartimento di Chimica Organica e Industriale, and Centro Interdisciplinare Materiali e Interfacce Nanostrutturati (CIMAINA) Università di Milano, via Venezian 21, 20133 Milano, Italy.
J Control Release. 2008 Feb 18;126(1):17-25. doi: 10.1016/j.jconrel.2007.11.004. Epub 2007 Nov 17.
A poly(amidoamine) (PAA) copolymer with beta-cyclodextrin was obtained by polyaddition reaction of 6-deoxy-6-amino-beta-cyclodextrin (beta-CD-NH(2)) and 2-methylpiperazine to 2,2-bis(acrylamido)acetic acid in aqueous medium. This beta-CD/PAA copolymer bears beta-CD units along the macromolecular chain, is water-soluble and non-cytotoxic. The complexing capacity of beta-CD/PAA was determined using an antiviral drug, Acyclovir, as a model of poorly water-soluble drug. Complex formation was confirmed by means of DSC and FTIR analyses. beta-CD/PAA can solubilize up to 11% w/w of Acyclovir notably increasing the aqueous solubility of the drug. The in vitro release studies showed the dependence of Acyclovir release rate on the solution pH. The antiviral activity of Acyclovir beta-CD/PAA complex was evaluated against herpes simplex virus type I in cell cultures. The Acyclovir beta-CD/PAA complex exhibited a higher antiviral activity than the free drug.
通过在水介质中使6-脱氧-6-氨基-β-环糊精（β-CD-NH₂）、2-甲基哌嗪与2,2-双（丙烯酰胺基）乙酸进行加成聚合反应，获得了一种含有β-环糊精的聚（酰胺胺）（PAA）共聚物。这种β-CD/PAA共聚物在大分子链上带有β-CD单元，具有水溶性且无细胞毒性。以抗病毒药物阿昔洛韦作为难溶性药物的模型，测定了β-CD/PAA的络合能力。通过差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）分析证实了络合物的形成。β-CD/PAA能够溶解高达11%（w/w）的阿昔洛韦，显著提高了该药物的水溶性。体外释放研究表明阿昔洛韦的释放速率取决于溶液的pH值。在细胞培养中评估了阿昔洛韦β-CD/PAA络合物对I型单纯疱疹病毒的抗病毒活性。阿昔洛韦β-CD/PAA络合物表现出比游离药物更高的抗病毒活性。
