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

Abstract

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 scattering, 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 in 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 characterization 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 obtained by different techniques confirm the feasibility of SpHL as a promising tool to PTX delivery in acidic environments, such as tumors.

Formulation Strategies for Folate-Targeted Liposomes and Their Biomedical Applications

“…A number of therapeutics, including paclitaxel (PTX) [105,106], doxorubicin (DOX) [107,108], methotrexate [109,110], cis-platin [111,112], curcumin [113,114], 5-fluorouracil [115,116], irinotecan [117,118], and nucleic acids [119,120], have been delivered via polymeric carriers [121] to cells. However, liposomes provide unique properties, as their charge, size, and surface properties can easily be tuned by selecting different ingredients of lipid mixture prior to the preparation of the liposomes.…”

Fast and Purification-Free Characterization of Bio-Nanoparticles in Biological Media by Electrical Asymmetrical Flow Field-Flow Fractionation Hyphenated with Multi-Angle Light Scattering and Nanoparticle Tracking Analysis Detection

“…Over the past years, both FFF and NTA have significantly grown in popularity for the analysis of complex biological samples including extracellular vesicles such as exosomes [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ], and liposomes [ 4 , 30 , 31 , 32 , 33 ]. It was therefore just a matter of time until both technologies were coupled in order to combine the advantages of both worlds.…”

<p>Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy</p>

“…Recently, many new drug delivery platforms for PTX, including prodrugs, 11 liposomes, 12 solid lipid nanoparticles 13 and polymeric micelles, 14 have emerged to circumvent the drawbacks of PTX. Polymeric micelles have been regarded as an effective nanoplatform because of their ability to encapsulate hydrophobic agents into their "coreshell" structure and deliver these agents to tumor regions by the enhanced permeability and retention (EPR) effect.…”