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Efficacy of a Poly‐ L ‐Glutamic Acid‐Gemcitabine Conjugate in Tumor‐Bearing Mice
Author(s) -
Kiew Lik Voon,
Cheong Soon Keng,
Ramli Ernidila,
Sidik Khalifah,
Lim Tuck Meng,
Chung Lip Yong
Publication year - 2012
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21012
Subject(s) - gemcitabine , in vivo , pharmacology , toxicity , pharmacokinetics , chemistry , carbodiimide , medicine , chemotherapy , biology , biochemistry , microbiology and biotechnology
trategy, Management and Health PolicyEnabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IVThis study assessed the in vivo antitumor efficacy of a polypeptide‐based poly‐ L ‐glutamic acid‐gemcitabine conjugate ( PG ‐ G ). PG ‐ G was synthesized by conjugating gemcitabine to poly‐L‐glutamic acid by a carbodiimide reaction. PG ‐ G was evaluated for its in vivo antitumor efficacy and toxicity using 4 T 1 murine breast tumor‐bearing mice. The antitumor effects of PG ‐ G were superior to those of unconjugated gemcitabine in both single and four‐consecutive dosing studies. Tumor regression was observed within 1 day after PG ‐ G administration and continued for 4–5 days. Thereafter, tumors grew at a slower rate compared with the unconjugated gemcitabine treatment group and other control groups. The main toxicity observed from the B erlin test was an apparent reversible weight loss of 10–12%. The unconjugated gemcitabine treatment group also demonstrated a similar, but reduced, weight loss trend. The present study demonstrates that the PG ‐ G formulation exhibits a significant antitumor activity in the aspects of tumor growth inhibition and shrinkage that is more robust than the parent drug and other control groups. Thus, the PG ‐ G dose regimen may be optimized to minimize side effects and render it a potential anticancer therapeutic.