title: PEGylated thermo-sensitive poly(amidoamine) dendritic drug delivery systems.
abstract: Thermo-sensitive dendrimers hold promise in various biomedical and pharmaceutical applications due to their stimuli-responsive properties. However, for such systems there are still certain unaddressed issues e.g. the undesired toxicity, immunogenicity and short blood circulation time. PEGylation is a potential approach to solve these above problems. The aims of this study were to engineer PEGylated thermo-sensitive dendritic derivatives and to investigate their temperature sensitivity and drug release behaviour therein. Linear poly(N-isopropylacrylamide) (PNIPAAm) and methoxy poly(ethylene glycol) (MPEG) were attached to the surface of polyamidoamine (PAMAM) dendrimers to generate PAMAM-g-PNIPAAm and PAMAM-g-PNIPAAm-co-PEG. PAMAM-g-PNIPAAm exhibited the lowest critical solution temperature (LCST) of ca. 32°C, whereas PAMAM-g-PNIPAAm-co-PEG showed a LCST of ca. 35°C. Indomethacin was used as a model molecule to examine the drug release profiles from both types of dendritic polymers. Results showed that such thermo-sensitive PAMAM derivatives could manipulate drug release simply by controlling the temperature above or below the LCST. At 37°C a prolonged drug release was obtained for both systems with less than 30% of drug was released over 12 h, whilst the release rate is much faster at 30°C and ca. 90% of drug was released over 12 h. The results obtained suggest that these thermo-sensitive PAMAM derivatives could be potential drug delivery systems to achieve controlled drug release.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiangpan
authors.initials: X
authors.lastname: Fan
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D007213:Indomethacin / Q000008:administration & dosage; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D000178:Acrylamides; D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D050091:Dendrimers; D004337:Drug Carriers; C531249:Poly(amidoamine); D011073:Polyamines; D011108:Polymers; C052970:poly-N-isopropylacrylamide; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D007213:Indomethacin