A 30 Kda Polyethylene Glycol-Enfuvirtide Complex Enhances The Exposure Of Enfuvirtide In Lymphatic Viral Reservoirs In Rats

Kaminskas, L, Williams, C, Leong, N, Chan, L, Butcher, N, Feeney, O, Porter, C, Tyssen, D, Tachedjian, G and Ascher, D 2019, 'A 30 Kda Polyethylene Glycol-Enfuvirtide Complex Enhances The Exposure Of Enfuvirtide In Lymphatic Viral Reservoirs In Rats', European Journal Of Pharmaceutics And Biopharmaceutics, vol. 137, pp. 218-226.


Document type: Journal Article
Collection: Journal Articles

Title A 30 Kda Polyethylene Glycol-Enfuvirtide Complex Enhances The Exposure Of Enfuvirtide In Lymphatic Viral Reservoirs In Rats
Author(s) Kaminskas, L
Williams, C
Leong, N
Chan, L
Butcher, N
Feeney, O
Porter, C
Tyssen, D
Tachedjian, G
Ascher, D
Year 2019
Journal name European Journal Of Pharmaceutics And Biopharmaceutics
Volume number 137
Start page 218
End page 226
Total pages 9
Publisher Elsevier
Abstract HIV therapy with anti-retroviral drugs is limited by the poor exposure of viral reservoirs, such as lymphoid tissue, to these small molecule drugs. We therefore investigated the effect of PEGylation on the anti-retroviral activity and subcutaneous lymphatic pharmacokinetics of the peptide-based fusion inhibitor enfuvirtide in thoracic lymph duct cannulated rats. Both the peptide and the PEG were quantified in plasma and lymph via ELISA. Conjugation to a single 5 kDa linear PEG decreased anti-HIV activity three-fold compared to enfuvirtide. Whilst plasma and lymphatic exposure to peptide mass was moderately increased, the loss of anti-viral activity led to an overall decrease in exposure to enfuvirtide activity. A 20 kDa 4-arm branched PEG conjugated with an average of two enfuvirtide peptides decreased peptide activity by six-fold. Plasma and lymph exposure to enfuvirtide, however, increased significantly such that anti-viral activity was increased two-and six-fold respectively. The results suggest that a multi-enfuvirtide-PEG complex may optimally enhance the anti-retroviral activity of the peptide in plasma and lymph.
Subject Pharmacology and Pharmaceutical Sciences not elsewhere classified
Keyword(s) PEGylation
Enfuvirtide
Lymphatic
Anti-viral
Pharmacokinetics
DOI - identifier 10.1016/j.ejpb.2019.03.008
Copyright notice © 2019 Elsevier B.V. All rights reserved.
ISSN 0939-6411
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