A comparison of covalent and noncovalent strategies for paclitaxel release using poly(ester amide) graft copolymer micelles

Abstract

Micelles formed from amphiphilic copolymers are promising for the delivery of drug molecules, potentially leading to enhanced properties and efficacies. Critical aspects of these systems include the use of biocompatible, biodegradable polymer backbones as well as the ability to control the incorporation of drugs and their release rates. In this work, a poly(ester amide)-poly(ethylene oxide) graft copolymer with paclitaxel conjugated via ester linkages was prepared and assembled into micelles. For comparison, micelles with physically encapsulated paclitaxel were also prepared. The release rates of these two systems were studied, and the micelles with covalently conjugated paclitaxel exhibited a prolonged release of the drug in comparison to the noncovalent system, which rapidly released the payload. In vitro studies suggested that the poly(ester amide)-poly(ethylene oxide) copolymers were nontoxic, whereas the toxicities of the drug-loaded micelles were dependent on their release rates. Overall, these systems are promising for further development as anticancer drug carriers.Résumé : Les micelles formées à partir de copolymères amphiphiles sont prometteuses dans le domaine de l'administration de molécules médicamenteuses et peuvent permettre d'améliorer les propriétés et l'efficacité de ces dernières. Les aspects essentiels de ces systèmes sont notamment l'utilisation de squelettes de polymères biocompatibles et biodégradables ainsi que la capacité à contrôler l'absorption de médicaments et leur vitesse de libération. Dans la présente étude, un copolymère greffé de poly(esteramide)-poly(oxyde d'éthylène) conjugué à du paclitaxel par l'intermédiaire de liaisons ester a été préparé et concentré sous forme de micelles. Des micelles constituées de paclitaxel physiquement encapsulé ont été également préparées à des fins de comparaison. Les vitesses de libération de ces deux systèmes ont été étudiées et les micelles conjuguées par liaisons covalentes à du paclitaxel ont permis une libération prolongée du médicament, contrairement au système non covalent, qui a rapidement libéré son contenu médicamenteux. Des études in vitro ont mis en évidence le fait que les copolymères de poly(esteramide)-poly(oxyde d'éthylène) étaient non toxiques et que la toxicité des micelles chargées en médicament dépendait de leurs vitesses de libération. Ces systèmes, utilisés comme vecteurs de médicaments anticancéreux, ont globalement des perspectives de dével-oppement encourageantes. [Traduit par la Rédaction]

Tracking Live‐Cell Response to Hexavalent Chromium Toxicity by using Scanning Electrochemical Microscopy

“…Since membrane permeability was observed to be affected by the additions of K 2 Cr 2 O 7 stressor, it was important to assessthe cellular viability of the cells. The use of a well‐established method of cell viability analysis, such as the MTT cell viability assay, provided a large scale determination of overall health and wellness of the T24 samples (Figure ). The healthy population of cells exposed to various concentrations of heavy metal stressor for 1 h, which were compared to the healthy population of an untreated sample from the same culture over the same timeframe [Eq.…”

Correlating Live Cell Viability with Membrane Permeability Disruption Induced by Trivalent Chromium

“…The effects of CrCl 3 on cellular viability were assessed using the MTT cell proliferation assay. , Briefly, 2 × 10 4 cells per well were seeded onto Corning Scientific Costar 96-well polystyrene flat bottom plates. After 24 h, the growth medium was aspirated and replaced with new growth medium containing CrCl 3 .…”

Degradable polyprodrugs: design and therapeutic efficiency

“…A PEA bearing pendant -COOH groups was produced by incorporating phenylalanine and aspartic acid as building blocks in the polymer backbone. 236,237 Post-conjugation of an anticancer drug floxuridine (Flox) 236 or a mixture of PEG and PTX 237 on the pendant -COOH groups could be achieved with carbodiimide coupling agents to afford polyprodrugs, respectively, with M w = 22 000 g mol À1 (Ð 1.7) or 100 000 g mol À1 (Ð 2.8) (Fig. 36).…”