Poly(lactide)-vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore.
Biomaterials (Impact Factor: 8.31). 04/2009; 30(19):3297-306. DOI: 10.1016/j.biomaterials.2009.02.045
Source: PubMed

ABSTRACT Four systems of nanoparticles of biodegradable polymers were developed in this research for oral delivery of anticancer drugs with Docetaxel used as a model drug, which include the poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), the poly(lactide)-vitamin E TPGS nanoparticles (PLA-TPGS NPs), the poly(lactic-co-glycolic acid)-montmorillonite nanoparticles (PLGA/MMT NPs) and the poly(lactide)-vitamin E TPGS/montmorillonite nanoparticles (PLA-TPGS/MMT NPs). Vitamin E TPGS stands for d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), which is a water-soluble derivative of natural vitamin E formed by esterification of vitamin E succinate with polyethylene glycol (PEG) 1000. The design was made to take advantages of TPGS in nanoparticle technology such as high emulsification effects and high drug encapsulation efficiency, and those in drug formulation such as high cellular adhesion and adsorption. MMT of similar effects is also a detoxifier, which may cure some side effects caused by the formulated drug. The drug-loaded NPs were prepared by a modified solvent extraction/evaporation method and then characterized for their MMT content, size and size distribution, surface charge and morphology, physical status and encapsulation efficiency of the drug in the NPs, and in vitro drug release profile. Cellular uptake of the coumarin 6-loaded NPs was investigated. In vitro cancer cell viability experiment showed that judged by IC(50), the PLA-TPGS/MMT NP formulation was found 2.89, 3.98, 2.12-fold more effective and the PLA-TPGS NP formulation could be 1.774, 2.58, 1.58-fold more effective than the Taxotere((R)) after 24, 48, 72h treatment, respectively. In vivo PK experiment with SD rats showed that oral administration of the PLA-TPGS/MMT NP formulation and the PLA-TPGS NP formulation could achieve 26.4 and 20.6 times longer half-life respectively than i.v. administration of Taxotere((R)) at the same 10mg/kg dose. One dose oral administration of the NP formulations could realize almost 3 week sustained chemotherapy in comparison of 22h of i.v. administration of Taxotere((R)). The oral bioavailability can be enhanced from 3.59% for Taxotere((R)) to 78% for the PLA-TPGS/MMT NP formulation and 91% for the PLA-TPGS NP formulation respectively. Oral chemotherapy by nanoparticles of biodegradable polymers is feasible.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Current guidelines recommend patients with active and mild-to-moderate ulcerative colitis (UC), who have received initial therapy with 5-aminosalicylic acid (5-ASA). In this study, a novel drug delivery vehicle achieved by pH-sensitive hydrogels was applied to 5-ASA. In our previous work, a novel P(CE-MAA-MEG) pH-sensitive hydrogel was successfully synthesized by the heat-initiated free radical polymerization method. The aim of this study is to investigate its site-specific delivering of drugs to the colon and evaluate its colon-targeting characteristic in vivo. 5-ASA was chosen as a model drug and successfully loaded in the hydrogel. In vitro investigations were carried out to evaluate its release process. Above all, animal treatment results reveal an obvious effect on the UC healing. Therefore, all results suggested that the developed 5-ASA-P(CE-MAA-MEG) hydrogel (5-ASA-GEL) as a colon-targeting vector might have a great potential application in the UC therapy.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2014.996924 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The aim of this work was to research the potential functions and the mechanism of absorption of the baicalin (BC)-loaded micelle system that contained Pluronic P123 copolymer (P123) and sodium taurocholate (ST) as carrier materials via oral delivery. Based on the numerous advantages of oral administration, such as cost-effectiveness, flexible and accommodated dosing regimen, and improved compliance for patients, the ST-P123-MMs system would be evaluated as oral delivery vehicle of BC. In this study, X-ray powder diffractometer analysis confirmed the phase change of BC after being incorporated in mixed micelles. The release study in simulated gastric fluid/simulated intestinal fluid exhibited that BC-loaded ST-P123-MMs presented a sustained drug release behavior. Compared with coumarin-6 solution, higher cellar uptake efficiency was achieved for coumarin-6 loaded ST-P123-MMs towards Caco-2 cell lines. The in situ perfusion test in rat indicated that the absorption of BC-loaded ST-P123-MMs in intestinal tract was stronger than BC solution. After oral administration, the Cmax and AUC of BC-loaded ST-P123-MMs were 1.77 times and 1.54 times as high as those of BC suspension in rat, respectively. Promisingly, the formulated BC exhibited a prolonged circulation time with the oral bioavailability increased to 1.54-fold compared with the control group. These results all suggested that P123 and ST mixed micelles could serve as a promising approach to oral administration of BC.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1008705 · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Microparticles (MPs) and nanoparticles (NPs) have received considerable attention for the design of drug delivery systems (DDS) with unique properties owing to the increased surface area and the ability to fine tune the release process. More recently, a new type of DDS that capitalize on the advantages of both NPs and MPs has been introduced. Nanoparticle-in-Microparticle Delivery Systems (NiMDS) comprise the encapsulation of NPs within MPs and lead to features that are unique and different from those of the individual components. These technology platforms can be produced employing from conventional to more sophisticated methodologies and equipment and they are administered by different routes such as oral, pulmonary or even parenteral. Moreover, if designed appropriately, “they can (i) protect drug payloads and prevent physical and chemical instability phenomena in the biological environment, (ii) improve the release profile of the encapsulated agent, (iii) reduce or eliminate the burst effect and (iv) target specific cells, tissues and organs.” Should be changed to “they can protect drug payloads and prevent physical and chemical instability phenomena in the biological environment, improve the release profile of the encapsulated agent, reduce or eliminate the burst effect and target specific cells, tissues and organs.”
    02/2013; 3(1):22-38. DOI:10.1166/jbt.2013.1064