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  • Title: PEGylated thermo-sensitive poly(amidoamine) dendritic drug delivery systems.
    Author: Zhao Y, Fan X, Liu D, Wang Z.
    Journal: Int J Pharm; 2011 May 16; 409(1-2):229-36. PubMed ID: 21316434.
    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.
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