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Well-Defined Star-Shaped Polyglutamates with Improved Pharmacokinetic Profiles As Excellent Candidates for Biomedical Applications
journal contribution
posted on 2015-10-05, 00:00 authored by Aroa Duro-Castano, Richard M. England, David Razola, Eduardo Romero, Marta Oteo-Vives, Miguel Angel Morcillo, María J. VicentThere
is a need to develop new and innovative polymer carriers
to be used as drug delivery systems and/or imaging agents owing to
the fact that there is no universal polymeric system that can be used
in the treatment of all diseases. Additionally, limitations with existing
systems, such as a lack of biodegradability and biocompatibility,
inevitably lead to side effects and poor patient compliance. New polymer
therapeutics based on amino acids are excellent candidates for drug
delivery, as they do not suffer from these limitations. This article
reports on a simple yet powerful methodology for the synthesis of
3-arm star-shaped polyglutamic acid with well-defined structures,
precise molecular weights (MW), and low polydispersity (Đ = <1.3). These were synthesized by ring-opening polymerization
(ROP) of N-carboxyanhydrides (NCA) in a divergent
method from novel multifunctional initiators. Herein, their exhaustive
physicochemical characterization is presented. Furthermore, preliminary
in vitro evaluation in selected cell models, and exhaustive in vivo
biodistribution and pharmacokinetics, highlighted the advantages of
these branched systems when compared with their linear counterparts
in terms of cell uptake enhancement and prolonged plasma half-life.
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Pharmacokinetic Profilesnovel multifunctional initiatorsside effectsacidcell modelsROPBiomedical ApplicationsTherepolymer carrierslimitationMWpatient compliancearticle reportsphysicochemical characterizationExcellent Candidatesvivo biodistributionNew polymer therapeuticsdrug delivery systemsdrug deliverycell uptake enhancementNCA
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