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Hydrogel Nanoparticles with Thermally Controlled Drug Release.

ABSTRACT: Improving the therapeutic efficacy and reducing systemic side effects of drugs is an important aspect in chemotherapy. The strategy presented here is the use of cisplatin loaded, temperature-sensitive, hydrogel nanoparticles (CisPt-NPs) and their ability to deliver and release chemodrugs selectively, based on thermal stimuli. The specially synthesized CisPt-NPs show a temperature-dependent increase of cisplatin release, at neutral pH (as in blood and normal tissue), in both the presence and absence of common metallic ions, as well as at the low pH found in lysosomes, where endocytosed NPs often localize. These CisPt-NPs were uptaken by breast cancer MDA-MB-435 cells, via endocytosis, and then mostly localized in the lysosomes. The in vitro cytotoxicity tests show that these CisPt-NPs have a significantly better efficacy at the slightly elevated temperatures. Potential applications are discussed.

SUBMITTER: Shirakura T

PROVIDER: S-EPMC4235390 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Hydrogel Nanoparticles with Thermally Controlled Drug Release.

Shirakura Teppei T Kelson Taylor J TJ Ray Aniruddha A Malyarenko Antonina E AE Kopelman Raoul R

ACS macro letters 20140612 7

Improving the therapeutic efficacy and reducing systemic side effects of drugs is an important aspect in chemotherapy. The strategy presented here is the use of cisplatin loaded, temperature-sensitive, hydrogel nanoparticles (CisPt-NPs) and their ability to deliver and release chemodrugs selectively, based on thermal stimuli. The specially synthesized CisPt-NPs show a temperature-dependent increase of cisplatin release, at neutral pH (as in blood and normal tissue), in both the presence and abse ...[more]

PMID: 25419487

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Project description:Nanotechnology-based drug delivery systems have been widely used for oral and systemic dosage forms delivery depending on the mucoadhesive interaction, and keratin has been applied for biomedical applications and drug delivery. However, few reports have focused on the keratin-based mucoadhesive drug delivery system and their mechanisms of mucoadhesion. Thus, the mucoadhesion controlled kerateine (reduced keratin, KTN)/keratose (oxidized keratin, KOS) composite nanoparticles were prepared via adjusting the proportion of KTN and KOS to achieve controlled gastric mucoadhesion and drug release based on their different mucoadhesive abilities and pH-sensitive properties. Furthermore, the mechanisms of mucoadhesion for KTN and KOS were also investigated in the present study.The composite keratin nanoparticles (KNPs) with different mass ratio of KTN to KOS, including 100/0 (KNP-1), 75/25 (KNP-2), 50/50 (KNP-3), and 25/75 (KNP-4), displayed different drug release rates and gastric mucoadhesion capacities, and then altered the drug pharmacokinetic performances. The stronger mucoadhesive ability of nanoparticle could supply longer gastric retention time, indicating that KTN displayed a stronger mucoadhesion than that of KOS. Furthermore, the mechanisms of mucoadhesion for KTN and KOS at different pH conditions were also investigated. The binding between KTN and porcine gastric mucin (PGM) is dominated by electrostatic attractions and hydrogen bondings at pH 4.5, and disulfide bonds also plays a key role in the interaction at pH 7.4. While, the main mechanisms of KOS and PGM interactions are hydrogen bondings and hydrophobic interactions in pH 7.4 condition and were hydrogen bondings at pH 4.5.The resulting knowledge offer an efficient strategy to control the gastric mucoadhesion and drug release of nano drug delivery systems, and the elaboration of mucoadhesive mechanism of keratins will enable the rational design of nanocarriers for specific mucoadhesive drug delivery.

Dataset Information

Hydrogel Nanoparticles with Thermally Controlled Drug Release.

Publications

Hydrogel Nanoparticles with Thermally Controlled Drug Release.

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