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. 2019 Dec;26(1):765-772.
doi: 10.1080/10717544.2019.1642420.

Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin

Muhammad Muzamil Khan  1   2 , Asadullah Madni  2 , Vladimir Torchilin  1 , Nina Filipczak  1   3 , Jiayi Pan  1 , Nayab Tahir  4 , Hassan Shah  2
Affiliations

Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin

Muhammad Muzamil Khan et al. Drug Deliv. 2019 Dec.

Abstract

Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipids and structural advantages of polymers can be obtained using this system for controlled drug delivery. In this study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratios were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. The stability of the formulation was demonstrated by thermal studies. Cytotoxicity and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays using the A2780 ovarian carcinoma cell line. The pharmacokinetics study in rabbits supported a controlled delivery of cisplatin with enhanced mean residence time and half-life. These studies suggest that cisplatin loaded LPHNP have promise as a platform for controlled delivery of cisplatin in cancer therapy.

Keywords: Cisplatin; chitosan; controlled release; lipid-polymer hybrid nanoparticles; ovarian cancer; pharmacokinetics.

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Figures

Figure 1.
Figure 1.
Transmission electron microscope image of lipid-polymer hybrid nanoparticles.
Figure 2.
Figure 2.
(A) Differential scanning calorimetry graphs of LPHNPs and its individual components against temperature. (B) Thermogravimetric analysis of LPHNPs and its individual components against temperature.
Figure 3.
Figure 3.
Cytotoxicity profile of cisplatin loaded LPHNPs and drug solution and blank LPHNPs after 24 hr (A) and 48 hr (B). All results indicate mean ± SD, n = 3. *p < .05, **p < .01, ***p < .001.
Figure 4.
Figure 4.
(A) Cell uptake of Rh-123 by the A2780 cell lines. All results indicate mean ± SD, n = 3, ***p < .001. (B) Fluorescence microscopy images of the A2780 cell line.
Figure 5.
Figure 5.
Concentration versus time profile curve of cisplatin LPHNPs and cisplatin solution (mean ± SD, n = 6).
See this image and copyright information in PMC

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