Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation (original) (raw)
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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.
Paclitaxel-loaded PCL–TPGS nanoparticles: In vitro and in vivo performance compared with Abraxane®
Colloids and Surfaces B: Biointerfaces, 2014
The purpose of this work was to develop Cremophor ® EL-free nanoparticles (NPs) loaded with Paclitaxel (PTX) in order to improve the drug i.v. pharmacokinetic profile and to evaluate its activity against commercially available formulations such as Taxol ® and Abraxane ® . PTX-loaded poly(-caprolactone)-alpha tocopheryl polyethylene glycol 1000 succinate (PCL-TPGS) NPs were prepared using three different techniques: (i) by nanoprecipitation (NPr-method), (ii) by emulsion-solvent evaporation homogenized with an Ultra-Turrax ® (UT-method) and (iii) by emulsion-solvent evaporation homogenized with an ultrasonicator (US-method). The NPs prepared by US-method showed the smallest size and the highest drug content. The NPs exhibited a slow and continuous release of PTX. The in vitro anti-tumoral activity was assessed using two human breast cancer cell lines (MCF-7 and MDA-MB-231) with the WTS assay. Cytotoxicity studies with both cell lines showed that PTX-loaded PCL-TPGS NPs exhibited better anti-cancer activity compared to PTX solution and the commercial formulation Abraxane ® at different concentrations. Importantly, in the case of triple negative MDA-MB-231 breast cancer cells, the IC 50 value for PTX-loaded PCL-TPGS NPs was 7.8 times lower than Abraxane ® . Finally, in vivo studies demonstrated that PTX-loaded PCL-TPGS NPs exhibited longer systemic circulation time and slower plasma elimination rate than Taxol ® and Abraxane ® . Therefore, the novel NPs investigated might be an alternative nanotechnological platform for PTX delivery system in cancer chemotherapy.
Bulletin of Materials Science, 2012
Clinical administration of paclitaxel is hindered due to its poor solubility, which necessitates the formulation of novel drug delivery systems to deliver such extreme hydrophobic drug. To formulate nanoparticles which makes suitable to deliver hydrophobic drugs effectively (intravenous) with desired pharmacokinetic profile for breast cancer treatment; in this context in vitro cytotoxic activity was evaluated using BT-549 cell line. PLGA nanoparticles were prepared by emulsion solvent evaporation technique and evaluated for physicochemical parameters, in vitro anti-tumor activity and in vivo pharmacokinetic studies in rats. Particle size obtained in optimized formulation was <200 nm. Encapsulation efficiency was higher at polymer-to-drug ratio of 20:1. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release (15 days). In vitro anti-tumor activity of optimized formulation inhibited cell growth for a period of 168 h against BT-549 cells. AUC (0−∞) and t 1/2 were found to be higher for nanoparticles with low clearance rate.
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.
Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2015
Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system. The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs surface by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed. The particle size of NPs ranged from 170 to 190 nm and increased about 20-30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased f...
Iranian journal of pharmaceutical research : IJPR, 2014
In this study a 3-factor, 3-level Box-Behnken design was used to prepare optimized docetaxel (DTX) loaded pegylated poly lactide-co-glycolide (PEG-PLGA) Nanoparticles (NPs) with polymer concentration (X1), drug concentration (X2) and ratio of the organic to aqueous solvent (X3) as the independent variables and particle size (Y1), poly dispersity index (PDI) (Y2) and drug loading (Y3) as the responses. The cytotoxicity of optimized DTX loaded PEG-PLGA NPs was studied in SKOV3 tumor cell lines by standard MTT assay. The in-vivo antitumor efficacy of DTX loaded PLGA-PEG NPs was assessed in tumor bearing female BALB/c mice. The optimum level of Y1, Y2 and Y3 predicted by the model were 188 nm, 0.16 and 9% respectively with perfect agreement with the experimental data. The in-vitro release profile of optimum formulation showed a burst release of approximately 20% (w/w) followed by a sustained release profile of the loaded drug over 288 h. The DTX loaded optimized nanoparticles showed a g...
A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer
Biomaterials, 2009
Paclitaxel (PTX) is one of the most effective chemotherapeutic drugs for the treatment of a variety of cancers. However, it is associated with serious side effects caused by PTX itself and the Cremophor EL emulsifier. In the present study, we report the development of a well-defined amphiphilic lineardendritic copolymer (named as telodendrimer) composed of polyethylene glycol (PEG), cholic acid (CA, a facial amphiphilic molecule) and lysine, which can form drug-loaded core/shell micelles when mixed with hydrophobic drug, such as PTX, under aqueous condition. We have used PEG 5k -CA 8 , a representive telodendrimer, to prepare paclitaxel-loaded nanoparticles (PTX-PEG 5k -CA 8 NPs) with high loading capacity (7.3 mg PTX/mL) and a size of 20-60 nm. This novel nanoformulation of PTX was found to exhibit similar in vitro cytotoxic activity against ovarian cancer cells as the free drug (Taxol Ò ) or paclitaxel/human serum albumin nanoaggregate (Abraxane Ò ). The maximum tolerated doses (MTDs) of PTX-PEG 5k -CA 8 NPs after single dose and five consecutive daily doses in mice were approximately 75 and 45 mg PTX/kg, respectively, which were 2.5-fold higher than those of Taxol Ò . In both subcutaneous and orthotopic intraperitoneal murine models of ovarian cancer, PTX-PEG 5k -CA 8 NPs achieved superior toxicity profiles and anti-tumor effects compared to Taxol Ò and Abraxane Ò at equivalent PTX doses, which were attributed to their preferential tumor accumulation, and deep penetration into tumor tissue, as confirmed by near infrared fluorescence (NIRF) imaging.
Materials Science and Engineering: C, 2018
Adenocarcinoma is the most lethal gynecologic tumor and treatment usually consists in surgery followed by chemotherapy. However, the chemotherapy benefits are eventually limited due to drug toxicity to normal tissues and cells, which cause several and harsh side effects. Paclitaxel (PCX) is the drug of first choice for ovarian cancer treatment, but it has low aqueous solubility, which reduces its bioavailability. Thus, in the commercial drug, Taxol ® , PCX is solubilized in a mixture of toxic surfactants. The development of drug nanocarriers has been investigated to promote the reduction of toxic effects and increase the safety and therapeutic efficacy of PCX. The aim of this work was the development and characterization of PCX loaded nanoparticles (PNPCX) and evaluation of in vitro efficacy of developed system using adenocarcinoma cell line. The nanocarrier was successfully obtained using nanoprecipitation technique. The results showed that the PNPCX-A had a particle size distribution around 140 nm and polydispersity index smaller than 0.1, with high PCX encapsulation efficiency. The results obtained were suitable for the intravenous administration route and promotion of passive targeting in the tumor microenvironment. The in vitro cytotoxicity assays of SKOV-3 cell line demonstrated that PNPCX-A was able to release PCX and reduce cell viability. The flow cytometry assays first reported that a nanostructured system with such composition (PNPCX-A) presented a time dependent cellular uptake, showing the ability of nanocarrier to be internalized. PNPCX-A present a distinguish potential for ovarian cancer therapy optimization. In vivo studies are needed to confirm the in vitro results and provide additional data regarding safety and efficacy of ovarian cancer treatment.
Anti-Cancer Drugs, 2015
Paclitaxel (PTX) is one of the most potent intravenous chemotherapeutic agents to date, yet an oral formulation has been problematic due to its low solubility and permeability. Using the recently discovered solubilizing properties of rubusoside (RUB), we investigated this unique PTX-RUB formulation. Paclitaxel was solubilized by RUB in water to levels of 1.6 to 6.3 mg/mL at 10 to 40% weight/volume. These, nanomicellar, PTX-RUB complexes were dried to a powder which was subsequently reconstituted in physiologic solutions. After 2.5 hrs in gastric fluid 85 to 99% of PTX-RUB remained soluble, while 79 to 96% remained soluble in intestinal fluid. The solubilization of PTX was mechanized by the formation of water-soluble spherical nanomicelles between PTX and RUB with an average diameter of 6.6 nm. Compared with Taxol ® , PTX-RUB nanoparticles were nearly four times more permeable in Caco-2 cell monocultures. In a side-byside comparison with DMSO-solubilized PTX, PTX-RUB maintained the same level of cytotoxicity against three human cancer cell lines with IC 50 values ranging from 4 nM to 20 nM. Additionally, tubular formation and migration of HUVECs were inhibited at levels as low as 5 nM. These chemical and biological properties demonstrated by the PTX-RUB nanoparticles may improve oral bioavailability and enable further pharmacokinetic, toxicologic, and efficacy investigations.