Phosphatidylserine targeting peptide-functionalized pH sensitive mixed micelles for enhanced anti-tumor drug delivery

Title

Phosphatidylserine targeting peptide-functionalized pH sensitive mixed micelles for enhanced anti-tumor drug delivery

Creator

Guan Siyu; Zhang Qianqian; Bao Jianwei; Duan Tijie; Hu Rongfeng; Czech Tori; Tang Jihui

Publisher

European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik e.V

Date

2019
2019-12-30

Description

In recent decades, targeted drug delivery systems (TDDS) have been widely used as an ideal method of improving therapeutic effects and reducing systemic side effects of chemotherapeutic agents. Historically, a handful of methods have been developed to further improve the targeting ability of delivery systems. Thus, in this study, two methods, taking advantage of tumor characteristics, were used for the creation of a multi-targeted delivery system. The first was the fabrication of pH-sensitive micelles, lending the ability to increase drug release by exploiting the acidic tumor environment. The second method was through utilization of the surface-exposed phosphatidylserine (PS) of tumors, which is normally found in the inner leaflet in healthy cells. Using PS as a target site, PS binding peptide (PSBP-6) was conjugated to pH-sensitive mixed micelles, (consisting of poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PDLLA) and poly (ethylene glycol)-b-poly (L-histidine) (PEG-PHIS)). After successful preparation of micelles, paclitaxel (PTX), a common chemotherapeutic agent, was selected to measure drug loading capacity and encapsulation efficiency, showing 7.9% and 83.5%, respectively. The in vitro release of PTX from mixed micelles at pH 5.0, 6.5, and 7.4 was 78.1, 56.8, and 51.4%, respectively, indicating acid-triggered drug release. The PSBP-6-modified, mixed micelles exhibited significantly enhanced in vitro cytotoxicity and demonstrated more efficient cellular uptake compared to unmodified mixed micelles in the HeLa cell line. Moreover, pharmacokinetic, in vivo biodistribution, and fluorescence imaging studies showed that PSBP-6-PEG-PDLLA/PEG-PHIS mixed micelles provide prolonged time in blood circulation and enhanced tumor accumulation. These results suggest that the use of PS as a novel targeting site is advantageous, and that these new multi-targeted mixed micelles show great potential for realization of broad prospects in the targeted treatment of tumors for chemotherapeutic delivery.

Subject

Drug delivery; pH-sensitive mixed micelles; Phosphatidylserine; Targeted peptide

Identifier

PMID: 31899369

Format

Journal Article

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

ISSN

1873-3441

NEOMED College

NEOMED College of Graduate Studies

NEOMED Department

NEOMED Student Publications; NEOMED College of Graduate Studies Student

Update Year & Number

January 2020 Update

Citation

Guan Siyu; Zhang Qianqian; Bao Jianwei; Duan Tijie; Hu Rongfeng; Czech Tori; Tang Jihui, “Phosphatidylserine targeting peptide-functionalized pH sensitive mixed micelles for enhanced anti-tumor drug delivery,” NEOMED Bibliography Database, accessed January 26, 2021, https://neomed.omeka.net/items/show/10932.

Social Bookmarking