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Nanoparticles of esterified polymalic acid for controlled anticancer drug release.

ABSTRACT: Esterification of microbial poly(malic acid) is performed with either ethanol or 1-butanol to obtain polymalate conjugates capable to form nanoparticles (100-350 nm). Degradation under physiological conditions takes place with release of malic acid and the corresponding alcohol as unique degradation products. The anticancer drugs Temozolomide and Doxorubicin are encapsulated in nanoparticles with efficiency of 17 and 37%, respectively. In vitro drug release assays show that Temozolomide is almost completely discharged in a few hours whereas Doxorubicin is steadily released along several days. Drug-loaded nano-particles show remarkable effectiveness against cancer cells. Partially ethylated poly(malic acid) nano-particles are those showing the highest cellular uptake.

SUBMITTER: Lanz-Landazuri A

PROVIDER: S-EPMC4159411 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Nanoparticles of esterified polymalic acid for controlled anticancer drug release.

Lanz-Landázuri Alberto A Portilla-Arias José J Martínez de Ilarduya Antxon A García-Alvarez Montserrat M Holler Eggehard E Ljubimova Julia J Muñoz-Guerra Sebastián S

Macromolecular bioscience 20140606 9

Esterification of microbial poly(malic acid) is performed with either ethanol or 1-butanol to obtain polymalate conjugates capable to form nanoparticles (100-350 nm). Degradation under physiological conditions takes place with release of malic acid and the corresponding alcohol as unique degradation products. The anticancer drugs Temozolomide and Doxorubicin are encapsulated in nanoparticles with efficiency of 17 and 37%, respectively. In vitro drug release assays show that Temozolomide is almos ...[more]

PMID: 24902676

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Project description:BackgroundLocal delivery of anti-cancer drugs through a stent is a very promising and anticipated treatment modality for patients who have obstructions in their gastrointestinal tract with malignant tumors. Anticancer drug release via stents, however, needs to be optimized with respect to drug delivery behavior for the stents to be effective for prolonged containment of tumor proliferation and stent re-obstruction. Local stent-based drug delivery has been tested using an effective anti-cancer drug, gemcitabine, but the release from the stent-coated polyurethane films is often too fast and the drug is depleted from the coated film virtually in a day.MethodsTo moderate the drug release from a polyurethane film, a gemcitabine-incorporated polyurethane film was enveloped with a pure polyurethane film, with no drug loading, and with a silicone film by solution casting after activation of the silicone film surface with plasma treatment.ResultsThe pure polyurethane barrier film was effective; the interface of the two were indistinguishable on scanning electron microscopy, and the initial burst, i.e., the cumulative release in a day, decreased from 90 to 26%. The silicone film barrier, on the other hand, was defective as voids were seen using a scanning electron microscope, and micro-separation of the two layers was observed after the film was immersed in phosphate-buffered saline for 1 day during the in vitro drug release study.ConclusionsEnveloping a gemcitabine-releasing polyurethane film with a homo-polymer barrier film was quite effective for moderating the initial burst of gemcitabine, thus, prolonging the release time of the drug. Enveloping the polyurethane film with a silicone film was also possible after plasma treatment of the silicone film surface, but the two films eventually separated in the aqueous environment. More studies are needed to tune the drug release behavior of gemcitabine from the stent covering film before attempting a clinical application of an anti-cancer drug releasing stent.

Dataset Information

Nanoparticles of esterified polymalic acid for controlled anticancer drug release.

Publications

Nanoparticles of esterified polymalic acid for controlled anticancer drug release.

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