Microfluidic Synthesis and Purification of Magnetoliposomes for Potential Applications in the Gastrointestinal Delivery of Difficult-to-Transport Drugs

Pharmaceutics

卷:14

Kevin A. Giraldo¹  Julian A. Serna¹  Carolina Muñoz-Camargo¹  Juan C. Cruz¹  Javier Cifuentes¹  Saúl C. Gómez¹  Valentina Quezada¹  Laura Rueda-Gensini¹  Paola Ruiz Puentes¹  Carlos E. Torres¹  Luis H. Reyes²  Johann F. Osma³ 

[1] Department of Biomedical Engineering, School of Engineering, Universidad de Los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia;

[2] Department of Chemical and Food Engineering, School of Engineering, Universidad de Los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia;

[3] Department of Electrical and Electronic Engineering, School of Engineering, Universidad de Los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia;

关键词: magnetoliposomes;    microfluidics;    oral drug delivery;    magnetite nanoparticles;   

DOI  :  10.3390/pharmaceutics14020315

来源: DOAJ

【 摘 要 】

Magnetite nanoparticles (MNPs) have gained significant attention in several applications for drug delivery. However, there are some issues related to cell penetration, especially in the transport of cargoes that show limited membrane passing. A widely studied strategy to overcome this problem is the encapsulation of the MNPs into liposomes to form magnetoliposomes (MLPs), which are capable of fusing with membranes to achieve high delivery rates. This study presents a low-cost microfluidic approach for the synthesis and purification of MLPs and their biocompatibility and functional testing via hemolysis, platelet aggregation, cytocompatibility, internalization, and endosomal escape assays to determine their potential application in gastrointestinal delivery. The results show MLPs with average hydrodynamic diameters ranging from 137 ± 17 nm to 787 ± 45 nm with acceptable polydispersity index (PDI) values (below 0.5). In addition, we achieved encapsulation efficiencies between 20% and 90% by varying the total flow rates (TFRs), flow rate ratios (FRRs), and MNPs concentration. Moreover, remarkable biocompatibility was attained with the obtained MLPs in terms of hemocompatibility (hemolysis below 1%), platelet aggregation (less than 10% with respect to PBS 1×), and cytocompatibility (cell viability higher than 80% in AGS and Vero cells at concentrations below 0.1 mg/mL). Additionally, promising delivery results were obtained, as evidenced by high internalization, low endosomal entrapment (AGS cells: PCC of 0.28 and covered area of 60% at 0.5 h and PCC of 0.34 and covered area of 99% at 4 h), and negligible nuclear damage and DNA condensation. These results confirm that the developed microfluidic devices allow high-throughput production of MLPs for potential encapsulation and efficient delivery of nanostructured cell-penetrating agents. Nevertheless, further in vitro analysis must be carried out to evaluate the prevalent intracellular trafficking routes as well as to gain a detailed understanding of the existing interactions between nanovehicles and cells.

【 授权许可】

Unknown