pH-Sensitive Polymer Nanospheres for Use as a Potential Drug Delivery Vehicle
ABSTRACT We report the development and characterization of pH-sensitive poly(2-tetrahydropyranyl methacrylate) [poly(THPMA)] nanospheres and demonstrate their feasibility as an effective drug delivery vehicle. Poly(THPMA) nanospheres were prepared using either the double emulsion or single emulsion method for the encapsulation of, respectively, water soluble (rhodamine B) or organic soluble (paclitaxel) payloads. The resulting nanospheres showed pH-dependent dissolution behavior, resulting in significant morphologic changes and loss of nanoparticle mass under mild acidic conditions (pH 5.1) with a half-life of 3.3 days, as compared to physiologic condition (pH 7.4) with a half-life of 6.2 days. The in vitro drug release profile of the paclitaxel-loaded poly(THPMA) nanospheres revealed that the rate of drug release in pH 5.1 acetate buffer was relatively faster than that in pH 7.4 HEPES buffer. Furthermore, poly(THPMA) nanospheres showed lower cytotoxicity and higher cellular uptake as compared to the FDA-approved PLGA-based nanospheres currently in clinical practice.
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- "Based upon physicochemical characteristics of these nanomicelles, we contemplate that these nanostructures can release the loaded drugs in the endosomal compartments in a pH-dependent manner. Similarly, pH-sensitive poly(2-tetrahydropyranyl methacrylate) [poly(THPMA)] nanospheres have recently been developed and shown higher cellular uptake potential with a pH-dependent release of the loaded drug (PTX) . Micellar formulation of PTX using cholesterol-grafted poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide-co-undecenoic acid) was reported to provide nanomicelles (~220 nm) with low CMC (~ 20 mg/L) and fast liberation of drug at pH 5.0 . "
ABSTRACT: Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU) polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells. The amphiphilic polyurethane was prepared through formation of urethane bounds between hydroxyl groups in poly (tetramethylene ether) glycol (PTMEG) and dimethylol propionic acid with isocyanate groups in toluene diisocyanate (TDI). The free isocyanate groups were blocked with phenol, while the free carboxyl groups of dimethylol propionic acid were reacted with triethylamine to attain ionic centers in the polymer backbone. These hydrophobic PTMEG blocks displayed self-assembly forming polymeric nanomicelles in water. The PTX loaded PU nanomicelles showed suitable physical stability, negative zeta potential charge (-43) and high loading efficiency (80%) with low level of critical micelle concentration (CMC). In vitro drug release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4, implying involvement of a pH-sensitive mechanism for drug release from the nanomicelles. The kinetic of release exquisitely obeyed the Higuchi model, confirming involvement of diffusion and somewhat erosion at pH 5.4. These nanomicelles significantly inhibited the growth and proliferation of the human breast cancer MCF-7 cells, leading them to apoptosis. The real time RT-PCR analysis confirmed the activation of apoptosis as result of liberation of cytochrome c in the cells treated with the PTX loaded PU nanomicelles. The comet assay analysis showed somewhat DNA fragmentation in the treated cells. Based upon these findings, we propose that the bioactive waterborne polyurethane nanomicelles can be used as an effective nanocarrier for delivery of anticancer chemotherapies such as paclitaxel.Journal of Nanobiotechnology 01/2012; 10(1):2. DOI:10.1186/1477-3155-10-2 · 4.12 Impact Factor
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ABSTRACT: Polymeric nanoparticles with unique properties are regarded as the most promising materials for biomedical applications including drug delivery and in vitro/in vivo imaging. Among them, stimulus-responsive polymeric nanoparticles, usually termed as “intelligent” nanoparticles, could undergo structure, shape, and property changes after being exposed to external signals including pH, temperature, magnetic field, and light, which could be used to modulate the macroscopical behavior of the nanoparticles. This paper reviews the recent progress in stimulus-responsive nanoparticles used for drug delivery and in vitro/in vivo imaging, with an emphasis on double/multiple stimulus-responsive systems and their biomedical applications. Keywordspolymer-stimulus-responsive nanoparticles-drug carrier-cellular imagingScience China-Chemistry 03/2010; 53(3):447-457. DOI:10.1007/s11426-010-0101-4 · 1.70 Impact Factor
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ABSTRACT: Within- and between-day stability in locomotor energy use was quantified in 13 children with hemiplegic cerebral palsy (CP). During testing, subjects were familiarized with the laboratory environment (Session 1), performed three 5 min level treadmill walks (Trials 1-3) at 0.67 m*s(-1) (Session 2), and completed a single 5 min walk (Trial 4) at 0.67 m*s(-1) (Session 3). In Sessions 2 and 3, heart rate (HR) was assessed and expired air was collected and analyzed to determine VO2. Data analyses revealed no significant difference (P > 0.05) in either net VO2 (ml kg(-1)*min(-1)) or EEI(HR) (b*m(-1)) across the three trials performed in Session 2 and between average measures of net VO2 and EEI(HR) quantified in Session 2 and those obtained in Session 3. Mean within-day coefficient of variation (CV) values for net VO2 and EEI(HR) were 8.6% +/- 8.5% and 13.9% +/- 7.8%, respectively. Analysis of between-day variability and energy expenditure revealed a between-day CV value of 13.1% for net VO2 and 24.0% for EEI(HR). In addition, significant inverse relationships between Gross Motor Function Measure (GMFM) scores and within- (r = -0.61) and between-day (r = -0.58) CV values for net VO2 were detected. Viewed in concert, these data suggest that fairly stable within- and between-day measures of locomotor energy expenditure during level treadmill walking can be achieved in subjects with hemiplegic CP if testing is preceded by a short period of treadmill accommodation. However, children with greater motor dysfunction may require an extended period of treadmill accommodation to reduce trial-to-trial variability in walking energy use.Gait & Posture 11/2005; 21(1):80-4. DOI:10.1016/j.gaitpost.2004.01.004 · 2.75 Impact Factor