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Low Systemic Toxicity Nanocarriers Fabricated From heparin-mPEG and PAMAM Dendrimers for Controlled Drug Release

Low Systemic Toxicity Nanocarriers Fabricated From heparin-mPEG and PAMAM Dendrimers for Controlled Drug Release

Vu Minh Thanh, Thi Hiep Nguyen, Tuong Vi Tran, Uyen-Thi Phan Ngoc, Minh Nhat Ho, Thi Thinh Nguyen, Yen Nguyen Tram Chau, Van Thu Le, Ngoc Quyen Tran, Cuu Khoa Nguyen, Dai Hai Nguyen

Mater Sci Eng C Mater Biol Appl. 2018 Jan 1;82:291-298.

PMID: 29025661

Abstract:

In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS76298	PAMAM-OH dendrimer, generation 4 solution			Price

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