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Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy.

ABSTRACT: One major challenge of current surface modification of nanoparticles is the demand for chemical reactive polymeric layers, such modification is always complicated, inefficient, and may lead the polymer lose the ability to encapsulate drug. To overcome this limitation, we adopted a pH-sensitive platform using polydopamine (PDA) as a way of functionalizing nanoparticles (NPs) surfaces. All this method needed to be just a brief incubation in weak alkaline solution of dopamine, which was simple and applicable to a variety of polymer carriers regardless of their chemical reactivity. We successfully conjugated the doxorubicin (DOX)-PDA-poly (lactic-co-glycolic acid) (PLGA) NPs with two typical surface modifiers: folate (FA) and a peptide (Arg-Gly-Asp, RGD). The DOX-PDA-FA-NPs and DOX-PDA-RGD-NPs (targeting nanoparticles) were characterized by particle size, zeta potential, and surface morphology. They were quite stable in various physiological solutions and exhibited pH-sensitive property in drug release. Compared to DOX-NPs, the targeting nanoparticles possessed an excellent targeting ability against HeLa cells. In addition, the in vivo study demonstrated that targeting nanoparticles achieved a tumor inhibition rate over 70%, meanwhile prominently decreased the side effects of DOX and improve drug distribution in tumors. Our studies indicated that the DOX-PLGA-NPs modified with PDA and various functional ligands are promising nanocarriers for targeting tumor therapy.

SUBMITTER: Bi D

PROVIDER: S-EPMC6058689 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy.

Bi Dongdong D Zhao Lei L Yu Runqi R Li Haowen H Guo Yifei Y Wang Xiangtao X Han Meihua M

Drug delivery 20181101 1

One major challenge of current surface modification of nanoparticles is the demand for chemical reactive polymeric layers, such modification is always complicated, inefficient, and may lead the polymer lose the ability to encapsulate drug. To overcome this limitation, we adopted a pH-sensitive platform using polydopamine (PDA) as a way of functionalizing nanoparticles (NPs) surfaces. All this method needed to be just a brief incubation in weak alkaline solution of dopamine, which was simple and ...[more]

PMID: 29457518

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Project description:BackgroundBased on the concept of "multimodal analgesia", a novel dual drug delivery system was designed to achieve synergistic analgesia between najanajaatra venom protein (αCT) and resveratrol (Res). In order to meet the joint loading of two drugs with different physicochemical properties without affecting each other, an oral Janus nanoparticle (JNP) with a unique cavity structure and synergistic drug delivery was constructed using an improved double emulsion solvent evaporation method, and combined with low-molecular-weight chitosan/sodium alginate and PLGA to achieve its pH-responsive.ResultsThe synthesized αCT/Res-JNPs are homogeneous in shape, with a two-compartment structure, approximately 230 nm in size, and zeta potential of 23.6 mV. Drug release assayed in vitro show that JNP was stable in simulated gastric juice (pH = 1.2) but was released in phosphate buffer saline (pH = 7.4). After intragastric administration in rats, PK evaluation showed that αCT/Res-JNPs could significantly improve the oral bioavailability, and the simultaneous encapsulation of the two drugs had no significant interaction on PK parameters. An obvious synergistic analgesic effects of αCT/Res-JNPs was confirmed in a spinal cord injury and acute pain model. Confocal laser scanning microscopy and single-pass intestinal perfusion model provided strong evidence that αCT/Res-JNPs could pass through intestinal epithelial cells, and the endocytosis pathway was mainly involved in the mediation and pinocytosis of reticulin. The concentrations of αCT and Res from αCT/Res-JNP in lymphatic transport were only about 8.72% and 6.08% of their blood concentrations at 1 h, respectively, which indicated that lymphatic transport in the form of JNP has limited advantages in improving the oral bioavailability of Res and αCT. Cellular uptake efficiency at 4 h was about 10-15% in Caco-2 cell lines for αCT/Res-JNP, but was reduced to 7% in Caco-2/HT29-MTX co-culture models due to the hindrance by the mucus layers. Approximately 12-17% of αCT/Res-JNP were transported across Caco-2/HT29-MTX/Raji monolayers. The cumulative absorption of JNP in three cell models was higher than that of free drug.ConclusionsThis study investigated the contribution of Janus nanoparticles in oral absorption, and provide a new perspective for oral administration and analgesic treatment of dual drug delivery system containing peptide drugs.

Dataset Information

Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy.

Publications

Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy.

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