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• W2092848002 abstract "Abstract A poly(ethylene glycol) (PEG) conjugate of 3′‐azido‐3′‐ deoxythymidine (AZT, zidovudine) was designed and synthesized as a novel sustained‐release prodrug. In the synthetic process, a succinate diester spacer was used to covalently couple AZT with methoxy poly(ethylene glycol) (mPEG; MW=2000). The conjugate was characterized by Fourier transform infrared (FTIR) and NMR spectroscopies and matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF) mass spectrometry (MS). The in vitro release was determined in hydrochloride (HCl) solution (pH 1.2) and phosphate‐buffered solution (PBS; pH 6.8), which showed the release rate of AZT from the conjugate was slower than that from the free drug, suggesting its possible increased retention in gastrointestinal conditions. Pharmacokinetic properties were evaluated experimentally by oral administration in mice. Compared to free AZT, the absorption half‐life ( t $_{{1over2}}$ ka ) and elimination half life ( t $_{{1over2}}$ β ) of AZT released from the conjugate were both extended to 0.51±0.03 h ( p <0.01) and 2.94±0.24 h ( p <0.01), respectively. Evaluation of the in vitro anti‐HIV activities showed mPEG‐AZT exhibited good inhibition of HIV‐1, with an EC 50 value of 0.0634 μ M , but it is lower than that of free AZT. These results show that the conjugate is capable of releasing the parent drug in a sustained profile, potentially providing a feasible alternative to oral administration of AZT in a clinical setting." @default.
• W2092848002 created "2016-06-24" @default.
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• W2092848002 date "2010-10-08" @default.
• W2092848002 modified "2023-10-05" @default.
• W2092848002 title "Synthesis, In Vitro and In Vivo Release Kinetics, and Anti-HIV Activity of A Sustained-Release Prodrug (mPEG-AZT) of 3′-Azido-3′-deoxythymidine (AZT, Zidovudine)" @default.
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• W2092848002 doi "https://doi.org/10.1002/cmdc.201000352" @default.
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