Nothapodytes burmanica Y.H.Tan & S.K.Shen, sp. nov. (Icacinaceae) from Kachin State, Myanmar is described and illustrated. It belongs to Nothapodytes due to the lorate hairy petals being connate at ...the base and a fleshy foliaceous disk divided into five leaflike lobes. Morphological and phylogenetic evidence indicates that it is close to N. pittosporoides. Morphologically, both species have oblanceolate or oblong leaf blades that are adaxially sparsely pubescent, but the new species is distinguished by its leaf base usually being oblique, and the paniculate inflorescence that has more numerous but smaller flowers with shorter petals. Phylogenetic results indicate that N. burmanica is deeply nested within the genus and forms a sister group of N. pittosporoides.
Abstract We developed a system of nanoparticles (NPs) of cholic acid functionalized, star-shaped block copolymer consisting of PLGA and vitamin E TPGS for sustained and controlled delivery of ...docetaxel for treatment of cervical cancer, which demonstrated superior in vitro and in vivo performance in comparison with the drug-loaded PLGA NPs and the linear PLGA- b -TPGS copolymer NPs. The star-shaped block copolymer CA-PLGA- b -TPGS of three branch arms was synthesized through the core-first approach and characterized by1 H NMR, GPC and TGA. The drug- or coumarin 6-loaded NPs were prepared by a modified nanoprecipitation technique and then characterized in terms of size and size distribution, surface morphology and surface charge, drug encapsulation efficiency, in vitro release profile and physical state of the encapsulated drug. The CA-PLGA- b -TPGS NPs were found to have the highest cellular uptake efficiency, the highest antitumor efficacy compared with PLGA- b -TPGS NPs and PLGA NPs. The results suggest that such a star-shaped copolymer CA-PLGA- b -TPGS could be used as a new molecular biomaterial for drug delivery of high efficiency.
Abstract Micelles may be the nanocarrier that is used most often in the area of nanomedicine due to its promising performance and technical simplicity. However, like the original drugs, micellar ...formulation may arouse intracellular autophagy that deteriorates their advantages for efficient drug delivery. There has been no report in the literature that involves the fate of micelles after successfully internalized into the cancer cells. In this study, we show by using docetaxel-loaded PEG- b -PLGA micelles as a micellar model that the micelles do arouse intracellular autophagy and are thus subject to degradation through the endo-lysosome pathway. Moreover, we show that co-administration of the micellar formulation with autophagy inhibitor such as chloroquine (CQ) could significantly enhance their therapeutic effects. The docetaxel-loaded PEG- b -PLGA micelles are formulated by the membrane dialysis method, which are of 7.1% drug loading and 72.8% drug encapsulation efficiency in a size range of around 40 nm with narrow size distribution. Autophagy degradation and inhibition are investigated by confocal laser scanning microscopy with various biological makers. We show that the IC50 values of the drug formulated in the PEG- b -PLGA micelles after 24 h treatment MCF-7 cancer cells with no autophagy inhibitor or in combination with CQ were 22.30 ± 1.32 and 1.75 ± 0.43 μg/mL respectively, which indicated a 12-fold more efficient treatment with CQ. The in vivo investigation further confirmed the advantages of such a strategy. The findings may provide advanced knowledge for development of nanomedicine for clinical application.
Abstract We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The ...latter plays a dual role as a pore-forming agent in the nanoparticles that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100–120 nm and EE ranged 85–95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC50 values of the free DTX and the DTX-loaded PLGA NPs of 0, 10, 20% TPGS were 2.619 and 0.474, 0.040, 0.009 μg/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs.
The recent progresses in tissue engineering and nanomaterial‐based therapeutics/theranostics have led to the ever increasing utilization of 3D in vitro experimental models as the bona fide culture ...systems to evaluate the therapeutic/theranostic effects of nanomedicine. Compared to the use of conventional 2D culture platforms, 3D biomimetic cultures offer unmatched advantages as relevant physiological and pathological elements can be incorporated to allow better characterization of the engineered bio‐nanomaterials in the targeted tissue‐specific microenvironment. In this Feature Article, the current state‐of‐the‐art 3D in vitro models that have been developed for the evaluation of biosafety and efficacy of nano‐ therapeutics/theranostics targeting the colon, blood–brain barrier (BBB), lungs, skin tumor models to bridge the nanomedicine bench to pre‐clinical ravine are reviewed. Furthermore, the critical physicochemical parameters of the bio‐nanomaterials that govern its transport and biodistribution in a complex 3D microenvironment will be highlighted. The major challenges and future prospects of evaluating nanomedicine in the third dimension will also be discussed.
In vitro 3D cell culture systems have emerged as important tools to evaluate the efficacy and toxicity of nano‐scale drug delivery vehicles. The use of 3D colon, blood brain barriers, lungs, skin, and tumor in vitro surrogates is here reviewed, to reveal salient insights that underpin the rational design of advanced nanomedicine.
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-α-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 IC50 , 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® after 24, 48, 72 h 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® at the same 10 mg/kg dose. One dose oral administration of the NP formulations could realize almost 3 week sustained chemotherapy in comparison of 22 h of i.v. administration of Taxotere® . The oral bioavailability can be enhanced from 3.59% for Taxotere® 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.
We report a facile strategy to synthesize folic acid-functionalized two-photon absorbing (TPA) nanoparticles with aggregation-induced emission for targeted cancer cell imaging using a two-photon ...fluorescence microscope.
The aim of this work was to investigate the effect of surface modification of biodegradable nanoparticles on their cellular uptake, cytotoxicity and biodistribution for the delivery of imaging and ...therapeutic agents across the blood-brain barrier.
Coumarin-6- and docetaxel-encapsulated poly(D,L-lactide-co-glycolide) nanoparticles were prepared by a modified single emulsion method using polyvinyl alcohol or D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) as emulsifier. The nanoparticles' surface was further modified with surfactants such as polysorbate-80 (Tween® 80), poloxamer 188 (F68) and poloxamer 407 (F127) to enhance cellular uptake of the NPs.
The F68-coated poly(D,L-lactide-co-glycolide) nanoparticles demonstrated the greatest cellular uptake and achieved highest fluorescence concentration in the brain tissues over those with T80 and F127 surface modification.
Surface modification is a feasible and efficient strategy for nanoparticles made of biodegradable polymers to deliver diagnostic and therapeutic agents across the blood-brain barrier.
Abstract A system of nanoparticles of mixed lipid monolayer shell and biodegradable polymer core was developed for targeted delivery of anticancer drugs with Docetaxel as a model drug, which provide ...targeting versatility with a quantitative control of the targeting effect by adjusting the lipid component ratio of the mixed lipid monolayer, and combine the advantages and avoid disadvantages of polymeric nanoparticles and liposomes in drug delivery. X-ray photoelectron spectroscopy (XPS) confirmed the coating of the mixed lipid monolayer on the polymeric core. Fluorescent microscopy proved the targeting efficacy of the folic acid conjugated on the mixed lipid monolayer for the cancer cells of over expression of folate receptors. The folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core were proved to possess sustainable, controlled and targeted delivery of anticancer drugs with Docetaxel as a model drug, which may provide a drug delivery system of precise control of the targeting effect.
Inflammatory bowel disease (IBD) is a chronic inflammatory disease involving the digestive tract, characterized by abdominal pain, diarrhea, rectal bleeding, and so on, which can make patients ...physically weakened and live difficultly. Although IBD has been recognized for many years, the pathogenesis of IBD has not yet been established and damage to intestinal barrier is thought to be closely associated with IBD. Intestinal barrier is an innate barrier that maintains the homeostasis of the intestinal environment and impedes pathogenic bacteria and toxins, and the endoplasmic reticulum (ER) has recently been found to be involved in maintaining the integrity of intestinal barrier. Endoplasmic reticulum stress (ERS) is a status of endoplasmic reticulum damaged when unfolded or misfolded proteins accumulate in excess of the degradation systematic clearance limit of the misfolded proteins. The regulation of ERS on protein folding synthesis and maintenance of cellular homeostasis is an important factor in influencing the integrity of the intestinal barrier. This paper mainly discusses the relationship between ERS and the intestinal barrier, aiming to understand the regulatory role of ERS on the intestinal barrier and the mechanism and to improve new solutions and notions for the treatment or prevention of IBD.
