Paclitaxel-Loaded pH-Sensitive Liposome: New Insights on Structural and Physicochemical Characterization

被引:47
作者
Monteiro, Liziane O. F. [1 ]
Malachias, Angelo [2 ]
Pound-Lana, Gwenaelle [4 ]
Magalhaes-Paniago, Rogerio [2 ]
Mosqueira, Vanessa C. F. [4 ]
Oliveira, Monica C. [1 ]
de Barros, Andre Luis B. [3 ]
Leite, Elaine A. [1 ]
机构
[1] Univ Fed Minas Gerais, Fac Farm, Dept Prod Farmaceut, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Dept Fis, Inst Ciencias Exatas, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Fac Farm, Dept Analises Clin, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil
[4] Univ Fed Ouro Preto, Lab Desenvolvimento Galen & Nanotecnol, Campus Univ Morro Cruzeiro, BR-35400000 Ouro Preto, MG, Brazil
关键词
DYNAMIC LIGHT-SCATTERING; 15-MER OLIGONUCLEOTIDE; CANCER-CHEMOTHERAPY; DRUG-DELIVERY; FRACTIONATION; THERAPEUTICS; FORMULATIONS; CIRCULATION; LAMELLAR; CARRIER;
D O I
10.1021/acs.langmuir.8b00411
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A long-circulating and pH-sensitive liposome containing paclitaxel (SpHL-PTX) was recently developed by our group. Once in an acidic environment, for example, tumors, these liposomes undergo destabilization, releasing the encapsulated drug. In this way, the aim of this study was to evaluate the molecular and supramolecular interactions between the lipid bilayer and PTX in similar biological environment conditions. High-sensitivity analyses of SpHL-PTX structures were obtained by the small-angle X-ray scattering technique combined with other techniques such as dynamic light scattenng, asymmetric flow field-flow fractionation, transmission electron microscopy, and high-performance liquid chromatography. The results showed that PTX incorporation in the liposomal bilayer clearly leads to changes m supramolecular organization of dioleoylphosphatidylethanolamine (DOPE) molecules, inducing the formation of more ordered structures. Changes in supramolecular organization were observed at lower pH, indicating that pH sensitivity was preserved even in the presence of fetal bovine serum proteins. Furthermore, morphological and physicochemical charactenzation of SpHL-PTX evidenced the formation of nanosized dispersion suitable for intravenous administration. In conclusion, a stable nanosized dispersion of PTX was obtained at pH 7.4 with suitable parameters for intravenous administration. At lower pH conditions, the pH sensitivity of the system was clearly evidenced by changes in the supramolecular organization of DOPE molecules, which is crucial for the delivery of PTX into the cytoplasm of the targeted cells. In this way, the results obtamed by different techniques confirm the feasibility of SpHL as a promising tool to PTX delivery in acidic environments, such as tumors.
引用
收藏
页码:5728 / 5737
页数:10
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