Polyaspartylhydrazide Copolymer-Based Supramolecular Vesicular Aggregates as Delivery Devices for Anticancer Drugs

Abstract

In this paper we report on three different hydrophilic copolymers based on alpha,beta-polyaspartylhydrazide (PAHy) bearing butyric groups in the side chain (C 4) (PAHy-C 4) or a combination of butyric groups and positive charged residues ((carboxypropyl)trimethylammonium chloride, CPTACl) (PAHy-C 4-CPTA) that were synthesized and used for the preparation of new supramolecular vesicular aggregates (SVAs) containing gemcitabine as an antitumor drug. Gemcitabine-loaded SVAs containing synthesized PAHy derivatives were characterized from the physicochemical and technological point of view and the in vitro toxicity and anticancer activity on two different human cancer cell lines, i.e., CaCo-2 (human colon carcinoma) and ARO (human anaplastic thyroid carcinoma) cells, were also evaluated. Moreover, considering that carrier-cell interaction is an important factor to achieve an improvement of anticancer drug activity, confocal laser scanning microscopy and flow cytometric experiments were carried out on the two different cancer cell lines.

Core-shell nanoparticulate formulation of gemcitabine: lyophilization, stability studies, and in vivo evaluation

“…Gemcitabine-loaded nanoparticles showed an IC 50 of 68.5, 64.7, and 16 μM on days 1, 2, and 3, respectively, while IC 50 of 30 μM was observed only after 3 days in the case of GEMCITE®. Similar results were also observed in the case of gemcitabine-loaded supramolecular vesicular aggregates (SVAs) wherein IC 50 for the nanovesicles was observed in 24 h in Caco 2 cells which have a doubling time of 32 h, while IC50 for free gemcitabine was not even achieved after 3 days [41]. Further, ultrastructural mechanistic studies of gemcitabine-loaded nano-vectors reported by Papa et al showed a distinct intracellular trafficking of nanoparticles resulting in mitochondrial, cytosolic, and endoplasmic reticulum stresses affecting the mechanism of drug action.…”

Folic acid-functionalized drug delivery platform of resveratrol based on Pluronic 127/D-α-tocopheryl polyethylene glycol 1000 succinate mixed micelles

“…[5][6][7] Recently, different classical and successful nanotherapeutics used to transport anticancer drugs into tumors have been fabricated and applied in order to improve the anticancer effect of chemotherapeutic drugs, the most prominent among which include polymeric nanocarriers such as liposomes, supramolecular derivatives and ultradeformable vesicles. [8][9][10] As one of the promising nanoparticular approaches, the mixed micelle carriers formed by triblock copolymers for delivery of anticancer drugs have been basically exploited in various clinical applications for the merits of smaller size, self-assembling ability, solubilization and protection against unstable drugs.…”

Folate-targeted supramolecular vesicular aggregates based on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs

“…We have recently proposed [8] a new generation of SVAs, which are characterized by a well-defined vesicular structure made up of dipalmitoylphosphatidylcholine, cholesterol plus a polymeric shell surrounding the vesicle made up of novel copolymeric derivatives of polyaspartyl-hydrazide (PAHy). The proposed SVAs are characterized by a strong and efficient integration of the polymeric moieties with the bilayer structure of vesicles through suitable alkyl pendant chains, thus providing a vesicular system with a modified surface [8].…”

“…The proposed SVAs are characterized by a strong and efficient integration of the polymeric moieties with the bilayer structure of vesicles through suitable alkyl pendant chains, thus providing a vesicular system with a modified surface [8]. In particular, the integration of PAHy copolymers together with the vesicular structure was not the result of the envelopment of the polymeric materials into the internal face of the vesicular membrane, as in the case of polymerosomes [5,7], but rather it depended exclusively on the physicochemical features of the PAHy derivatives [9e11], which elicited the process of self-assemblage into a vesicular structure.…”