Microfluidic Synthesis of Vinblastine-Loaded Multifunctional Particles for Magnetically Responsive Controlled Drug Release

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2019 May 7

PMID 31058849

Citations 9

Authors

Keng-Shiang Huang

Chih-Hui Yang

Ya-Chin Wang

Wei-Ting Wang

Yen-Yi Lu

Affiliations

Soon will be listed here.

Abstract

Vinblastine (VBL) is a major chemotherapeutic drug; however, in some cases, it may cause severe side effects in patients with cancer. Designing a novel VBL pharmaceutical formulation is a crucial and emerging concern among researchers for reducing the use of VBL. This study developed a stimuli-responsive controlled VBL drug release system from magnetically sensitive chitosan capsules. A magnetically responsive controlled drug release system was designed by embedding superparamagnetic iron oxide (SPIO) nanoparticles (NPs) in a chitosan matrix and an external magnet. In addition, droplet microfluidics, which is a novel technique for producing polymer spheres, was used for manufacturing monodispersed chitosan microparticles. The prepared VBL and SPIO NPs-loaded chitosan microparticles were characterized and analyzed using Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, a superconducting quantum interference device, and a biocompatibility test. The drug encapsulation efficiency was 67%-69%. The in vitro drug release test indicated that the VBL could be 100% released from chitosan composite particles in 80-130 min under magnetic stimulation. The pulsatile magnetically triggered tests showed individual and distinctive controlled release patterns. Thus, the timing and dose of VBL release was controllable by an external magnet. The results presume that using a magnetically responsive controlled drug release system offers a valuable opportunity for VBL drug delivery, where the delivery system is an active participant, rather than a passive vehicle, in the optimization of cancer treatment. The proposed actively targeted magnetic drug delivery system offers many advantages over conventional drug delivery systems by improving the precision and timing of drug release, easy operation, and higher compliance for pharmaceutical applications.

Citing Articles

Microfluidically Assisted Synthesis of Calcium Carbonate Submicron Particles with Improved Loading Properties.

Ermakov A, Chapek S, Lengert E, Konarev P, Volkov V, Artemov V Micromachines (Basel). 2024; 15(1).

PMID: 38276844 PMC: 10818696. DOI: 10.3390/mi15010016.

Chitosan-Based Particulate Carriers: Structure, Production and Corresponding Controlled Release.

Weng J, Durand A, Desobry S Pharmaceutics. 2023; 15(5).

PMID: 37242694 PMC: 10221392. DOI: 10.3390/pharmaceutics15051455.

Recent Advances in Drug Delivery System Fabricated by Microfluidics for Disease Therapy.

Jia F, Gao Y, Wang H Bioengineering (Basel). 2022; 9(11).

PMID: 36354536 PMC: 9687342. DOI: 10.3390/bioengineering9110625.

Facile synthesis of highly tunable monodispersed calcium hydroxide composite particles by using a two-step ion exchange reaction.

Yang C, Wang Y, Wang T, Chang Y, Lin Y, Chen P RSC Adv. 2022; 10(23):13700-13707.

PMID: 35493011 PMC: 9051553. DOI: 10.1039/d0ra01275k.

Advances in Magnetic Nanoparticles Engineering for Biomedical Applications-A Review.

Baki A, Wiekhorst F, Bleul R Bioengineering (Basel). 2021; 8(10).

PMID: 34677207 PMC: 8533261. DOI: 10.3390/bioengineering8100134.

References

Yang S, Guo F, Kiraly B, Mao X, Lu M, Leong K . Microfluidic synthesis of multifunctional Janus particles for biomedical applications. Lab Chip. 2012; 12(12):2097-102. PMC: 6365143. DOI: 10.1039/c2lc90046g. View

Zheng G, Zhang X, Yang Y, Zeng S, Wei J, Wang Y . An integrated microfludic device for culturing and screening of Giardia lamblia. Exp Parasitol. 2013; 137:1-7. DOI: 10.1016/j.exppara.2013.11.009. View

Lin W . Introduction: Nanoparticles in Medicine. Chem Rev. 2015; 115(19):10407-9. DOI: 10.1021/acs.chemrev.5b00534. View

Lin Y, Huang K, Yang C, Wang C, Yang Y, Hsu H . Microfluidic synthesis of microfibers for magnetic-responsive controlled drug release and cell culture. PLoS One. 2012; 7(3):e33184. PMC: 3314645. DOI: 10.1371/journal.pone.0033184. View

Zu Y, Zhang Y, Zhao X, Zhang Q, Liu Y, Jiang R . Optimization of the preparation process of vinblastine sulfate (VBLS)-loaded folate-conjugated bovine serum albumin (BSA) nanoparticles for tumor-targeted drug delivery using response surface methodology (RSM). Int J Nanomedicine. 2010; 4:321-33. PMC: 2802044. DOI: 10.2147/ijn.s8501. View

Yang C, Huang K, Wang C, Hsu Y, Chang F, Lin Y . Microfluidic-assisted synthesis of hemispherical and discoidal chitosan microparticles at an oil/water interface. Electrophoresis. 2012; 33(21):3173-80. DOI: 10.1002/elps.201200211. View

Yang F, Wang H, Hu P, Jiang J . Validation of an UPLC-MS-MS Method for Quantitative Analysis of Vincristine in Human Urine After Intravenous Administration of Vincristine Sulfate Liposome Injection. J Chromatogr Sci. 2014; 53(6):974-8. DOI: 10.1093/chromsci/bmu164. View

Zhang X, Zhao X, Zu Y, Chen X, Lu Q, Ma Y . Preparation and physicochemical properties of vinblastine microparticles by supercritical antisolvent process. Int J Mol Sci. 2012; 13(10):12598-607. PMC: 3497290. DOI: 10.3390/ijms131012598. View

Dandamudi S, Campbell R . The drug loading, cytotoxicty and tumor vascular targeting characteristics of magnetite in magnetic drug targeting. Biomaterials. 2007; 28(31):4673-83. DOI: 10.1016/j.biomaterials.2007.07.024. View

10.

Lee C, Huang Y, Yang C, Huang K . Drug delivery systems and combination therapy by using vinca alkaloids. Curr Top Med Chem. 2015; 15(15):1491-500. PMC: 4997956. DOI: 10.2174/1568026615666150414120547. View

11.

Huang K, Shieh D, Yeh C, Wu P, Cheng F . Antimicrobial applications of water-dispersible magnetic nanoparticles in biomedicine. Curr Med Chem. 2014; 21(29):3312-22. DOI: 10.2174/0929867321666140304101752. View

12.

Hou X, Zhang H, Li H, Zhang D . Magnetic albumin immuno-nanospheres as an efficient gene delivery system for a potential use in lung cancer: preparation, in vitro targeting and biological effect analysis. J Drug Target. 2015; 24(3):247-56. DOI: 10.3109/1061186X.2015.1070857. View

13.

Veloso S, Ferreira P, Martins J, Coutinho P, Castanheira E . Magnetogels: Prospects and Main Challenges in Biomedical Applications. Pharmaceutics. 2018; 10(3). PMC: 6161300. DOI: 10.3390/pharmaceutics10030145. View

14.

Seid C, Fidler I, Clyne R, Earnest L, Fan D . Overcoming murine tumor cell resistance to vinblastine by presentation of the drug in multilamellar liposomes consisting of phosphatidylcholine and phosphatidylserine. Sel Cancer Ther. 1991; 7(3):103-12. DOI: 10.1089/sct.1991.7.103. View

15.

Yang C, Huang K, Lin Y, Lu K, Tzeng C, Wang E . Microfluidic assisted synthesis of multi-functional polycaprolactone microcapsules: incorporation of CdTe quantum dots, Fe3O4 superparamagnetic nanoparticles and tamoxifen anticancer drugs. Lab Chip. 2009; 9(7):961-5. DOI: 10.1039/b814952f. View

16.

Osswald H . [Potentiation of the chemotherapeutic effect of vinblastine by thymidine]. Arzneimittelforschung. 1972; 22(8):1421. View

17.

Samperiz M, BLUMEN G, MERZEL J . Effect of vinblastine on the cell cycle and migration of ameloblasts of mouse incisors as shown by autoradiography using 3H-thymidine. Cell Tissue Kinet. 1985; 18(5):493-503. DOI: 10.1111/j.1365-2184.1985.tb00691.x. View

18.

Marinina J, Shenderova A, Mallery S, Schwendeman S . Stabilization of vinca alkaloids encapsulated in poly(lactide-co-glycolide) microspheres. Pharm Res. 2000; 17(6):677-83. DOI: 10.1023/a:1007522013835. View

19.

Yang C, Wang C, Huang K, Kung C, Chang Y, Shaw J . Microfluidic one-step synthesis of Fe₃O₄-chitosan composite particles and their applications. Int J Pharm. 2013; 463(2):155-60. DOI: 10.1016/j.ijpharm.2013.08.020. View

20.

Deng L, Ren J, Li J, Leng J, Qu Y, Lin C . Magnetothermally responsive star-block copolymeric micelles for controlled drug delivery and enhanced thermo-chemotherapy. Nanoscale. 2015; 7(21):9655-63. DOI: 10.1039/c5nr00642b. View