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Lipid-polymer hybrid nanoparticles for controlled delivery of hydrophilic and lipophilic doxorubicin for breast cancer therapy

Authors Tahir N, Madni A, Correia A, Rehman M, Balasubramanian V, Khan MM, Santos HA

Received 19 March 2019

Accepted for publication 14 May 2019

Published 5 July 2019 Volume 2019:14 Pages 4961—4974

DOI https://doi.org/10.2147/IJN.S209325

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Thiruganesh Ramasamy

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster


Nayab Tahir,1–3 Asadullah Madni,2 Alexandra Correia,3 Mubashar Rehman,4 Vimalkumar Balasubramanian,3 Muhammad Muzamil Khan,2 Hélder A Santos3,5

1College of Pharmacy, University of Sargodha, Sargodha, Pakistan; 2Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; 3Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland; 4Department of Pharmacy, The University of central Pujnab, Lahore, Pakistan; 5Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki FI-00014, Finland

Background: Lipid polymer hybrid nanoparticles (LPHNPs) for the controlled delivery of hydrophilic doxorubicin hydrochloride (DOX.HCl) and lipophilic DOX base have been fabricated by the single step modified nanoprecipitation method.
Materials and methods: Poly (D, L-lactide-co-glicolide) (PLGA), lecithin, and 1,2-distearoyl-Sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000 (DSPE-PEG 2000) were selected as structural components.
Results: The mean particle size was 173–208 nm, with an encapsulation efficiency of 17.8±1.9 to 43.8±4.4% and 40.3±0.6 to 59. 8±1.4% for DOX.HCl and DOX base, respectively. The drug release profile was in the range 33–57% in 24 hours and followed the Higuchi model (R2,=0.9867–0.9450) and Fickian diffusion (n<0.5). However, the release of DOX base was slower than DOX.HCl. The in vitro cytotoxicity studies and confocal imaging showed safety, good biocompatibility, and a higher degree of particle internalization. The higher internalization of DOX base was attributed to higher permeability of lipophilic component and better hydrophobic interaction of particles with cell membranes. Compared to the free DOX, the DOX.HCl and DOX base loaded LPHNPs showed higher antiproliferation effects in MDA-MB231 and PC3 cells.
Conclusion: Therefore, LPHNPs have provided a potential drug delivery strategy for safe, controlled delivery of both hydrophilic and lipophilic form of DOX in cancer cells.

Keywords: lipid polymer hybrid, doxorubicin, breast cancer, nanotechnology, drug delivery


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