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. 2019 Dec;26(1):724-731.
doi: 10.1080/10717544.2019.1639845.

Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate

Wen Lin  1 , Xiaoxing Ma  2 , Chaopei Zhou  3 , Hong Yang  4   5 , Yang Yang  2   3   6 , Xiangyang Xie  5 , Chunrong Yang  3 , Cuiyan Han  2
Affiliations

Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate

Wen Lin et al. Drug Deliv. 2019 Dec.

Abstract

The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the in vitro and in vivo studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

Keywords: Ultrasound sensitivity; control release; drug delivery system; sonodynamic effect; sonosensitizer.

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Figures

Figure 1.
Figure 1.
In vitro release of VIN-loaded SL (6% HMME) with different ultrasound irradiated time in PBS (0.1 M, pH 7.4) at 37 °C (A). In vitro release of VIN-loaded SL and VIN-loaded NL with or without ultrasound in PBS (0.1 M, pH 7.4) at 37 °C (B). The data are presented as the means ± SD (n = 3). * indicates p < .05.
Figure 2.
Figure 2.
Particle size distribution of VIN-loaded SL (A). Morphological appearance of VIN-loaded SL based on TEM (B). In vitro release of VIN from various liposomal formulations in PBS (0.1 M, pH 7.4) at 37 °C (C). In vitro release of VIN-loaded SL and VIN-loaded NL with ultrasound after a 24-h incubation in PBS (0.1 M, pH 7.4) at 37 °C (D). The data are presented as the means ± SD (n = 3).formulations in PBS (0.1 M, pH 7.4) at 37 °C (C). In vitro release of VIN-loaded SL and VIN-loaded NL with ultrasound after a 24-h incubation in PBS (0.1 M, pH 7.4) at 37 °C (D). The data are presented as the means ± SD (n = 3).
Figure 3.
Figure 3.
Plasma VIN concentration-time profiles after i.v. injection of different formulations in rat (n = 3) (A). Concentration of VIN in the major organs 0.5 h after i.v. injection (B). The data are presented as the means ± SD (n = 3). * indicates p < .05.
Figure 4.
Figure 4.
Antitumor activity (A) and survival curve (B) in MCF-7 tumor-bearing mice after treatments with 5% glucose, free VIN and varying formulations carrying VIN. The data are presented as the means ± SD (n = 10). * indicates p < .05.
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Grants and funding

We are grateful for the financial support from Beijing NSF (Grant No. 7172162), NSF (Grant No. 81874305), Heilongjiang NSF (Grant No. H2015070), Health & Family Planning Commission of Hubei Province (Grant No. WJ2017Q031) and Young & Middle-aged Medical Key Talents Training Project of Wuhan (Grant No. 2018-6).

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