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- W3100681429 abstract "Dendrimers are novel nanoscale sized macromolecules that have a well-defined highly branched structure and a large number of reactive chain-ends. Here the potential use of dendrimers as an oral drug delivery system has been evaluated. First experiment designed to assess the in vitro biocompatibility of cationic branched polymers; poly(vinylamine)(vinylformamide) (PVF) copolymers and two different classes of dendrimers; diaminoethane (DAE) and polyamidoamine (PAMAM) dendrimers of different generation (Mw 289-50,865 Da) and different surface characteristics (-COONa, -NH2). The haemolysis of PVF copolymers is increased as a function of amine content. Dendrimers with an amine surface were generally toxic depending on their concentration and generation. In contrast, dendrimers with carboxylate surface were shown to be biocompatible. Non-toxic PAMAM dendrimers were radioiodinated and used to investigate their ability to traverse rat intestinal tissue in vitro. The rate of serosal transfer and tissue uptake for anionic dendrimers was in the range of 3.4-4.4 and 0.6-2.5 μl/mg protein/h, respectively, whereas for cationic dendrimers these values were in the range of 2.3-2.7 and 3.3-4.8 μl/mg protein/h. After oral administration in vivo, most of the dose recovered was found in stomach and small intestine in 1 h, and after 5 h entered the caecum and colon. By 24 h most radioactivity (70-90% of the recovered dose) was located in faeces. The amount of radioactivity found in the blood was insignificant (0.1- 1%). As 10-30% of the administered dose was not found in the organs studied the extent of oral absorption of dendrimer is so far inconclusive. Finally studies were carried out using PAMAM dendrimers to investigate their ability to complex with piroxicam and indomethacin. Dendrimer gen 3 formed complexes with both drugs in aqueous solution. However, the interaction showed insufficient control of drug release to allow in vivo application. Therefore, a preliminary study was conducted to synthesis and characterise covalent drug-dendrimer conjugates using ibuprofen as a model drug. Overall the observations made in these studies show that dendrimers do have potential as drug carriers for oral delivery and in future dendrimers must be more specifically designed to promote oral absorption and subsequent controlled release." @default.
- W3100681429 created "2020-11-23" @default.
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- W3100681429 date "1999-01-01" @default.
- W3100681429 modified "2023-09-23" @default.
- W3100681429 title "Evaluation of dendrimers as a potential oral drug delivery system" @default.
- W3100681429 hasPublicationYear "1999" @default.
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