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The delivery of drugs is a great challenge, since most of active pharmaceutical ingredients developed today are hydrophobic and poorly water soluble. From this perspective, drug encapsulation on biodegradable and biocompatible polymers can surpass this problem. Poly(gamma-glutamic acid) (PGGA), a bioedible and biocompatible polymer has been chosen for this purpose. Carboxylic side groups of PGGA have been partially esterified with 4-phenyl-butyl bromide, producing a series of aliphatic–aromatic ester derivatives with different hydrophilic–lipophilic balances. Using nanoprecipitation or emulsion/evaporation methods, these copolymers were self-assembled in a water solution, forming nanoparticles with average diameters between 89 and 374 nm and zeta potential values between -13.1 and -49.5 mV. The hydrophobic core containing 4-phenyl-butyl side groups was used for the encapsulation of an anticancer drug, such as Doxorubicin (DOX). The highest encapsulation efficiency was reached for a copolymer derived from PGGA, with a 46 mol % degree of esterification. Drug release studies carried out for 5 days at different pHs (4.2 and 7.4) indicated that DOX was released faster at pH 4.2, revealing the potential of these nanoparticles as chemotherapy agents., Peer Reviewed, Postprint (published version)

One of the treatments for cancer is chemotherapy but most anticancer drugs have a low therapeutic index, which causes toxicity complications in the healthy tissues [1]. To minimize these complications and improve the effect of the existing drugs, drug delivery by nanoparticles have drawn more attention as they are easy to produce and can also be prepared through biocompatible polymers [2]. Here, we report the preparation of polymer nanoparticles derived from esters of poly(¿-glutamic acid) which could be able to encapsulate hydrophobic drugs that can be used as drug delivery systems (DDS) for the treatment of different tumours. In this work, PGGA has been modified in order to improve its solubility in organic solvents and its processing capacity of this water-soluble polymer. Due to the fact that most of the anticancer drugs are lipophilic, the hydrophobic modification of PGGA will enhance the drug encapsulation., Postprint (published version)

We report a novel approach for the modular and convergent construction of biocompatible graft copolymers starting from bacterial poly(¿-glutamic acid)(¿-PGA) and incorporating poly(lactic acid) (PLA). This synthesis strategy is controlled at different levels: (a) the choice of a suitable initiator for the ring-opening polymerization of lactide; (b) the chemical elaboration of the polylactic fragments; and (c) their convergent “grafting to” functionalization of bacterial ¿-PGA propargyl ester using copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) click chemistry. The graft copolymers are characterized in terms of their thermal and macromolecular properties, their conformational preferences through molecular modelling, and their cytotoxicity., Peer Reviewed, Objectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats Sostenibles, Postprint (author's final draft)

Poly(gamma-glutamic acid) (gamma-PGA) is one of the few bacterial polymers in nature; as such, it possesses the added value of a “green birth” (fermentation) and “green death” (biodegradability), which is ideal for sustainable macromolecular platforms. Efficient functionalization strategies are required in order to transform the native bacterial biopolymer into a material with tailored properties for bulk scale or biomedical applications. We report on a novel approach to the facile functionalization of bacterial gamma-PGA, realized with several levels of control: (a) the modulation of the molecular weight through sonication, and the solubilization in organic solvents through counterion exchange with suitable quaternary ammonium salts, (b) the introduction of reactive functionalities through reactions in homogeneous conditions in organic solvents, to afford homo- or copolymers; (c) a second tier functionalization using copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) click chemistry., Peer Reviewed, Postprint (published version)

A series of ionic complexes with a comb-like architecture and a nearly stoichiometric composition were prepared from bacterial poly(gamma,dl-glutamic acid) (PGGA) and alkyltrimethyl phosphonium bromides (nATMP·Br) bearing long linear alkyl chains with even numbers of carbon atoms (n) ranging from 12 to 22. The nATMP·PGGA complexes were non-water soluble but readily soluble in organic solvents, and they displayed a high thermal stability. Combined DSC and XRD studies revealed that these complexes adopted an amphiphilic layered structure with the polypeptide chain and the alkyl chain separated in two differentiated phases with a nanoperiodicity that increased steadily with the length of the alkyl chain. The paraffinic phase was found to be partially crystallized in an extent that decreased with n, so that complexes with n = 12 and 14 did not show any sign of crystallinity whereas those with n from 16 to 22 showed crystalline melting in the ~30–70 °C range. The structural transitions taking place by temperature effects were characterized by simultaneous SAXS/WAXS using synchrotron radiation at real time. In all cases, a shortening of the layer periodicity occurred upon heating with recovering of the initial structure after cooling. nATMP·PGGA with n = 16 showed strong antimicrobial activity against both E. coli and S. aureus, a property that could be related to the weak dissociation of the complexes happening upon incubation in water. The structure and properties of these complexes where comparatively discussed taking as reference their analog complexes made from PGGA and alkyltrimethylammonium bromides already studied by us., Peer Reviewed, Postprint (author's final draft)

Comb-like ionic complexes were prepared from polyuronic acids (pectinic and alginic acids) and alkyltrimethylammonium surfactants bearing linear alkyl chains with 18, 20 and 22 carbon atoms. In the condensed state, these complexes were able to self-assemble in ordered structures which were thermally stable up to ~200ºC. The complexes were analysed by DSC and WAXS/SAXS and compared to their analogous made from poly(γ-glutamic acid). They all adopt a biphasic layered structure in which the main chain and the alkyl side chain alternate with a nanometric periodicity. Alkyl side chains were partially crystallized in these complexes and they show reversible melting at temperatures within the 60-80ºC range depending on the length of the polymethylene segment., Peer Reviewed, Postprint (published version)