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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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1573-904X

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The Effect of Molecular Weight Drug Load and Cha

Authors: ChaoSheng Chen Clyde M Ofner
Publish Date: 2008/10/31
Volume: 26, Issue: 2, Pages: 338-345
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Abstract

Gelatin 34 to 171 kDa was reacted with a carbodiimide to prepare GMTX with high GMTXH and low GMTXL drug loads Cationic conjugates were prepared by ethylenediamine modification MTXgelatin molar ratios were determined spectrophotometricaly Isoelectric focusing electrophoresis IEF and turbidity were used to measure isoelectric points IEP Growth inhibition profiles and IC50 values were determined on HL60 cells using a modified MTT assayIC50 values of anionic GMTXL drug loads 051 to 221 increased linearly from 46 to 180 nM with MW But IC50 values for anionic GMTXH drug loads 741 to 251 showed little if any MW dependence and were about two times higher IC50 values for cationic GMTXL ranged from 770 to 2900 nM and the relationship with MW was nonlinearThe growth inhibition ranking was MTX anionic GMTXL anionic GMTXH cationic GMTXL High drug load may hinder lysosomal enzyme degradation and drug release and contribute to suppression of the MW effect observed with GMTXL A mechanism change is suggested as the cationic conjugates increase to the highest MW

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