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 (original) (raw)
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Molecules
The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS-block-poly(ε-caprolactone) (TPGS-b-PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS-b-PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1–5 kDa), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. Assembly of block copolymers was achieved via the cosolvent evaporation method. The self-assembled structures were characterized for their size, polydispersity, and CMC using dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the succ...
Nanoscale research letters, 2014
Block copolymers composed of poly(3-hydroxyoctanoate) (PHO) and methoxy poly(ethylene glycol) (PEG) were synthesized to prepare paclitaxel-incorporated nanoparticle for antitumor drug delivery. In a (1)H-NMR study, chemical structures of PHO/PEG block copolymers were confirmed and their molecular weight (M.W.) was analyzed with gel permeation chromatography (GPC). Paclitaxel as a model anticancer drug was incorporated into the nanoparticles of PHO/PEG block copolymer. They have spherical shapes and their particle sizes were less than 100 nm. In a (1)H-NMR study in D2O, specific peaks of PEG solely appeared while peaks of PHO disappeared, indicating that nanoparticles have core-shell structures. The higher M.W. of PEG decreased loading efficiency and particle size. The higher drug feeding increased drug contents and average size of nanoparticles. In the drug release study, the higher M.W. of PEG block induced the acceleration of drug release rate. The increase in drug contents induce...
Journal of Advanced Zoology, 2023
The effectiveness of paclitaxel as a cancer treatment is widely recognized. However, its solubility issue can be addressed by blending it with ethanol and Cremophor EL, a product marketed under the trade name Taxol. Nevertheless, to enhance the anticancer efficacy of Cremophor EL and reduce adverse effects, alternative delivery methods and strategies must be explored. The objective of this work was to synthesize PLGA nanoparticles (PNF) loaded with paclitaxel and evaluate a number of characteristics, including in vitro drug release, drug loading, polydispersity index, zeta potential, and particle size. Finding the best formulation, PNF4, based on its in vitro drug release properties, was the main goal of the study. The surface morphology of PNF4 was then investigated by means of scanning and transmission electron microscopy after that (SEM and TEM). The delivery method follows the Korsmeyer-Peppas model, according to analysis of the in vitro drug release kinetics, indicating a "Fickian diffusion" mechanism. Furthermore, the in vitro cytotoxicity assessment demonstrated that the PNF4 formulation exhibited superior cytotoxicity compared to free paclitaxel.
Journal of Peptide Science, 2013
This study covers the preparation of microspheres for the controlled and targeted release of paclitaxel, using novel degradable polymers as carrier materials. Paclitaxel-loaded microspheres were prepared by oil-in-water single-emulsion solvent extraction/evaporation technique by using a series of polyurethanes and a block copolymer; the physicochemical properties of these polymers were modulated by changing nature and composition of their structural units. The obtained microparticles showed a regular morphology and properties (diameter: 1-100 mm; resuspension index: 18.8-100%; encapsulation efficiency: 26.6-97.2%) depending on polymer hydrophilicity and emulsifier used. In vitro release curves showed in all cases almost zero-order kinetics after an initial low burst effect (from 1 to 8.4%), which is required to minimize the drug side effects. This work also proposes a novel strategy to combine a controlled and a targeted release through the functionalization of the polymer matrix with peptide sequences. An RGD-functionalized polyurethane was used to successfully prepare paclitaxel-loaded microparticles. Studies on the preparation of polymer microspheres are reported.
Colloids and surfaces. B, Biointerfaces, 2018
An amphiphilic block copolymer poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) was evaluated as a carrier for therapeutic delivery of paclitaxel (PTX). PEO-PBO and PTX form nanoparticles (NPs) by self-assembly upon hydration. The size of these NPs was about 92.71nm and the zeta potential was -5.06mV, which met the requirements for passive tumor targeting through the enhanced permeability and retention effect. Compared with a commonly used block copolymer poly(ethylene glycol)-b-poly-D,L-(lactic acid) (PEG-PDLLA), PEO-PBO forms nanoparticles with superior pharmacokinetic, biodistribution, and tumor inhibitory properties. Meanwhile, results of hemolysis study and CMC determination showed that PEO-PBO had better biocompatibility and stability than PEG-PDLLA. These data suggest that PEO-PBO has potential for application in drug delivery and warrant further evaluation.
Pharmaceutical Research, 2008
Purpose. Develop a Cremophor \ and solvent free formulation of paclitaxel using amphiphilic block copolymer micelles of poly(ethylene glycol)-b-poly((-caprolactone) (PEG-b-PCL) and characterize their release, solubility, cytotoxicity, tolerability, and disposition. Methods. Hydrophobic prodrugs of paclitaxel were synthesized via DCC/DMAP or anhydride chemistry to overcome the poor loading (<1% w/w) of paclitaxel in micelles of PEG-b-PCL. Micelles were prepared by a co-solvent extraction technique. A micellar formulation of paclitaxel prodrug (PAX7 ¶C 6 ) was dosed intravenously to rats (10 mg/kg) and compared to Taxol \ (paclitaxel in CrEL:EtOH) and PAX7 ¶C 6 in CrEL:EtOH as controls at the same dose. Pharmacokinetic parameters and tissue distribution were assessed. Results. Paclitaxel prodrugs had solubilities >5 mg/ml in PEG-b-PCL micelles. Resulting PEG-b-PCL micelles contained 17-22% w/w prodrug and were less than 50 nm in diameter. PEG-b-PCL micelles released paclitaxel prodrugs over several days, t 1/2 >3 d. Only the 7 ¶derivative of paclitaxel with the shortest acylchain 7 ¶hexonoate (PAX7 ¶C 6 ) maintained cytotoxic activity similar to unmodified paclitaxel. PAX7 ¶C 6 micelles demonstrated an increase in area under the curve, half-life, and mean residence time while total clearance and volume of distribution decreased. Conclusions. Paclitaxel prodrugs in PEG-b-PCL micelle nanocarriers augment the disposition and increase tolerability making further studies on tumor efficacy warranted.
Paclitaxel-Containing Nano-Engineered Polymeric Capsules Towards Cancer Therapy
Journal of Nanoscience and Nanotechnology, 2009
Paclitaxel is one of the anticancer agents most often used in clinical oncology practice for the treatment of ovarian, breast and non-small cell lung cancers. Nanoengineered polymeric capsules (NPCs) represent a new and very effective tool for the encapsulation and smart release of different compounds. In present work capsules were fabricated by means of the layer-by-layer assembly of oppositely charged polyelectrolytes onto colloidal particles, followed by removal of the cores at low pH to obtain hollow microcapsules. Paclitaxel was loaded into the capsule. As tumors exhibit a lower extracellular pH than normal tissues, the property of NPCs to open the pores in their shell at slightly acidic pH values could be used for the triggered release of paclitaxel within a tumor microenvironment. For the characterization of NPCs, quartz crystal microbalance was to monitor the process of shell growth on planar supports. The effective encapsulation of paclitaxel was then demonstrated by atomic force microscopy and micro-Raman spectroscopy, whereas its release was characterized by Uv-vis spectroscopy. Finally the biological activity of encapsulated paclitaxel against human breast cancer cells was assessed.
A Novel Nanoparticle Formulation for Sustained Paclitaxel Delivery
AAPS PharmSciTech, 2008
To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Methods. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). Results. These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC 50 of PTX. Conclusion. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.
Bioresorbable microspheres as devices for the controlled release of paclitaxel
naun.org
The release of the anti-cancer drug paclitaxel (PTX) from microspheres of both a bioresorbable poly(ε-caprolactoneoxyethylene-ε-caprolactone) tri-block copolymer and of polyurethanes containing either copolymers with the same composition and different molecular weights or poly(ε-caprolactone) diol as soft segments was studied. The microspheres, both loaded and not with PTX, were prepared by emulsion-evaporation technique, then characterized by SEM and DSC. The quantities of PTX released were measured by HPLC. The results showed slow and very regular releases, which fit very well the Peppas equation, M t /M ∞ = k • t n , where M t is the amount of solute released at the time t, M ∞ is the amount of drug released at the plateau condition, k represents the Peppas kinetic constant and n the diffusion order. Most n values are consistent with non-Fickian release mechanisms, with the exceptions of two less hydrophilic polyurethanes.