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
Open Access
- 11 December 2020
- journal article
- research article
- Published by MDPI AG in Nanomaterials
- Vol. 10 (12), 2490
- https://doi.org/10.3390/nano10122490
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.Keywords
This publication has 75 references indexed in Scilit:
- Synthesis of biocompatible poly(ε-caprolactone)-block-poly(propylene adipate) copolymers appropriate for drug nanoencapsulation in the form of core-shell nanoparticlesInternational Journal of Nanomedicine, 2011
- Solid dispersions, Part II: new strategies in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugsExpert Opinion on Drug Delivery, 2011
- Facile synthesis of polyester-PEG triblock copolymers and preparation of amphiphilic nanoparticles as drug carriersJournal of Controlled Release, 2010
- A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-PuThe Journal of Chemical Physics, 2010
- Metal–organic frameworks as potential drug carriersCurrent Opinion in Chemical Biology, 2010
- Novel self-assembled core–shell nanoparticles based on crystalline amorphous moieties of aliphatic copolyesters for efficient controlled drug releaseJournal of Controlled Release, 2009
- Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO2, and their nanocomposites as appropriate drug carriersDrug Development and Industrial Pharmacy, 2009
- Microwave-induced enhancement of the dissolution rate of poorly water-soluble tibolone from poly(ethylene glycol) solid dispersionsJournal of Applied Polymer Science, 2008
- A post-Hartree–Fock model of intermolecular interactionsThe Journal of Chemical Physics, 2005
- Solid dispersion particles of tolbutamide prepared with fine silica particles by the spray-drying methodPowder Technology, 2004