Dissolution Enhancement and Controlled Release of Paclitaxel Drug via a Hybrid Nanocarrier Based on mPEG-PCL Amphiphilic Copolymer and Fe-BTC Porous Metal-Organic Framework

Abstract

In the present work, the porous metal-organic framework (MOF) Basolite®F300 (Fe-BTC) was tested as a potential drug-releasing depot to enhance the solubility of the anticancer drug paclitaxel (PTX) and to prepare controlled release formulations after its encapsulation in amphiphilic methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) nanoparticles. Investigation revealed that drug adsorption in Fe-BTC reached approximately 40%, a relatively high level, and also led to an overall drug amorphization as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The dissolution rate of PTX-loaded MOF was substantially enhanced achieving a complete (100%) release within four days, while the neat drug only reached a 13% maximum rate (3–4 days). This PTX-Fe-BTC nanocomposite was further encapsulated into a mPEG-PCL matrix, a typical aliphatic amphiphilic copolyester synthesized in our lab, whose biocompatibility was validated by in vitro cytotoxicity tests toward human umbilical vein endothelial cells (HUVEC). Encapsulation was performed according to the solid-in-oil-in-water emulsion/solvent evaporation technique, resulting in nanoparticles of about 143 nm, slightly larger of those prepared without the pre-adsorption of PTX on Fe-BTC (138 nm, respectively). Transmission electron microscopy (TEM) imaging revealed that spherical nanoparticles with embedded PTX-loaded Fe-BTC nanoparticles were indeed fabricated, with sizes ranging from 80 to 150 nm. Regions of the composite Fe-BTC-PTX system in the infrared (IR) spectrum are identified as signatures of the drug-MOF interaction. The dissolution profiles of all nanoparticles showed an initial burst release, attributed to the drug amount located at the nanoparticles surface or close to it, followed by a steadily and controlled release. This is corroborated by computational analysis that reveals that PTX attaches effectively to Fe-BTC building blocks, but its relatively large size limits diffusion through crystalline regions of Fe-BTC. The dissolution behaviour can be described through a bimodal diffusivity model. The nanoparticles studied could serve as potential chemotherapeutic candidates for PTX delivery.

Sustainable One-Pot Immobilization of Enzymes in/on Metal-Organic Framework Materials

“…Fe-BTC provides enough stability to retain the enzyme activity and biocatalyst performance (i.e., See Figure 3, the relative catalytic activity of GOx, LIP and ADH is maintained during 5 reaction cycles). Future work could be devoted to testing the performance of other enzymes integrated in a cascade system [70] or even other classes of macromolecules [96,97] and to verify the feasibility of a continuous processes by using a continuous fixed-bed reactor or on larger-scale production.…”

Combined Shikonin-Loaded MPEG-PCL Micelles Inhibits Effective Transition of Endothelial-to-Mesenchymal Cells

“…However, the application of shikonin is limited by its low water solubility and poor bioavailability. Amphipathic di-block copolymer of MPEG-PCL exhibited good biocompatibility in various cytotoxicity studies [35][36][37][38] and in vivo studies. 39 It was considered as a promising drug delivery system for hydrophobic drugs.…”

Programmable Drug Release from a Dual-Stimuli Responsive Magnetic Metal–Organic Framework

“…The rapid release under weakly acidic pH could result from MOFs' structural decomposition due to linker protonation. 68,69 To confirm this, the FT-IR spectra of FeMn-MIL-88B MOFs (before and after) immersed in pH 5.4 solution for 24 h and free linker were compared. As shown in Figure 5B, a shift in the antisymmetric and symmetric bands of the coordinated linker from 1597 and 1365 cm −1 to 1627 and 1277 cm −1 in the acid-exposed MOFs hints at the protonation of the linker.…”