Improving aqueous solubility of paclitaxel with polysarcosine-b-poly(γ-benzyl glutamate) nanoparticles.

Autor: Lebleu C; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Plet L; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Moussy F; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Gitton G; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Da Costa Moreira R; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Guduff L; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Burlot B; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Godiveau R; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Merry A; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Lecommandoux S; Univ. Bordeaux, CNRS, Bordeaux INP, LCPO, UMR 5629, F-33600 Pessac, France., Errasti G; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Philippe C; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Delacroix T; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France., Chakrabarti R; PMC Isochem SAS, 32, rue Lavoisier F-91710, Vert-Le-Petit, France; Chakrabarti Advanced Technology, LLC, PMC Group Building, 1288 Route 73, Ste 110, Mount Laurel, NJ 08054, USA. Electronic address: raj@pmc-group.com.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Jan 25; Vol. 631, pp. 122501. Date of Electronic Publication: 2022 Dec 16.
DOI: 10.1016/j.ijpharm.2022.122501
Abstrakt: New stealth amphiphilic copolymers based on polysarcosine (PSar) rather than poly(ethylene glycol) (PEG) have gained more attention for their use as excipients in nanomedicine. In this study, several polysarcosine-b-poly(γ-benzyl glutamate) (PSar-b-PGluOBn) block copolymers were synthesized by ring opening polymerization (ROP) of the respective N-carboxyanhydrides (NCAs) and were characterized by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance ( 1 H NMR) and size-exclusion chromatography (SEC). Copolymers had different PGluOBn block configuration (racemic L/D, pure L or pure D), degrees of polymerization of PSar between 28 and 76 and PGluOBn between 9 and 93, molar masses (M n ) between 5.0 and 24.6 kg.mol -1 and dispersities (Đ) lower than 1.4. Nanoparticles of PSar-b-PGluOBn loaded with paclitaxel (PTX), a hydrophobic anti-cancer drug, were obtained by nanoprecipitation. Their hydrodynamic diameter (D h ) ranged from 27 to 118 nm with polydispersity indexes (PDI) between 0.01 and 0.20, as determined by dynamic light scattering (DLS). Their morphology was more spherical for copolymers with a racemic L/D PGluOBn block configuration synthesized at 5 °C. PTX loading efficiency was between 63 and 92 % and loading contents between 7 and 15 %. Using PSar-b-PGluOBn copolymers as excipients, PTX apparent water-solubility was significantly improved by a factor up to 6600 to 660 µg.mL -1 .
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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