title: Transdermal delivery of nonsteroidal anti-inflammatory drugs mediated by polyamidoamine (PAMAM) dendrimers.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs in the world, primarily for symptoms associated with osteoarthritis and other chronic musculoskeletal conditions. However, adverse effects caused by oral administration, such as local or systemic disturbance in the gastrointestinal tract, have limited the clinical applications of these drugs. In the present study we have assessed the ability of polyamidoamine (PAMAM) dendrimers to facilitate transdermal delivery of NSAIDs, using Ketoprofen and Diflunisal as model drugs. In vitro permeation studies with excised rat skins indicated that PAMAM dendrimers significantly enhanced the accumulative permeated amount of both drugs after 24 h, as compared to drug suspensions without PAMAM dendrimers. Similarly, anti-nociceptive studies using the acetic acid-induced writhing model in mice showed a prolonged pharmacodynamic profile for the NSAIDs-PAMAM dendrimer complex after transdermal administration. In addition, blood drug level studies revealed that the bioavailability was 2.73 times higher for the Ketoprofen-PAMAM dendrimer complex and 2.48 times higher for the Diflunisal-PAMAM dendrimer complex, respectively, than the pure drug suspensions. These results demonstrated that PAMAM dendrimers can effectively facilitate skin penetration of NSAIDs and may have the potential applications for the development of new transdermal formulations.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China. yycheng@mail.ustc.edu.cn
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
authors.forename: Na
authors.initials: N
authors.lastname: Man
authors.forename: Tongwen
authors.initials: T
authors.lastname: Xu
authors.forename: Rongqiang
authors.initials: R
authors.lastname: Fu
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Longping
authors.initials: L
authors.lastname: Wen
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D050091:Dendrimers; D004061:Diflunisal / Q000008:administration & dosage*; D007660:Ketoprofen / Q000008:administration & dosage*; D011073:Polyamines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D004061:Diflunisal; D007660:Ketoprofen