Synthesis, characterization, and evaluation of a novel amphiphilic polymer RGD-PEG-Chol for target drug delivery system.

An amphiphilic polymer RGD-PEG-Chol which can be produced in large scale at a very low cost has been synthesized successfully. The synthesized intermediates and final products were characterized and confirmed by ¹H nuclear magnetic resonance spectrum (¹H NMR) and Fourier transform infrared spectrum (FT-IR). The paclitaxel- (PTX-) loaded liposomes based on RGD-PEG-Chol were then prepared by film formation method. The liposomes had a size within 100 nm and significantly enhanced the cytotoxicity of paclitaxel to B16F10 cell as demonstrated by MTT test (IC50 = 0.079 µg/mL of RGD-modified PTX-loaded liposomes compared to 9.57 µg/mL of free PTX). Flow cytometry analysis revealed that the cellular uptake of coumarin encapsulated in the RGD-PEG-Chol modified liposome was increased for HUVEC cells. This work provides a reasonable, facile, and economic approach to prepare peptide-modified liposome materials with controllable performances and the obtained linear RGD-modified PTX-loaded liposomes might be attractive as a drug delivery system.

Ternary PtZrNi nanorods for efficient multifunctional electrocatalysis towards oxygen reduction and alcohol oxidation.

Pt-based alloys with precise structure and composition design have been considered to be effective and robust novel electrocatalysts for fuel cells. Whereas, the sluggish kinetics of oxygen reduction reaction (ORR) and low intrinsic activity of Pt limited their real application on a large scale. Herein, a novel ternary PtZrNi nanorods (PtZrNi NRs) was synthesized via a facile wet-chemical method to achieve high electrocatalytic performance for both ORR and alcohol oxidation reaction owing to the synergism of chosen three elements and prominent one-dimensional morphology. Specifically, the PtZrNi NRs show enhanced mass and specific activities of 0.755 A mgPt-1 and of 0.97 mA/cm2 at 0.9 VRHE towards ORR in acidic media, which are 4.7 and 4.4 times of those of commercial Pt/C, respectively. Additionally, in alkaline media, the PtZrNi NRs also exhibit superior ORR mass and specific activities of 3.216 A mgPt-1and 4.13 mA/cm2, enhanced by 34.6 and 31.3 times compared with those of commercial Pt/C, respectively. The PtZrNi NRs retain the nanorod shape well without agglomeration after an accelerated durability test (20000 cycles). This work may offer a new perspective for engineering high-performance Pt-based electrocatalysts for commercial fuel cells.

Determination of free and encapsulated cytarabine and daunorubicin in rat plasma after intravenous administration of liposomal formulation using ultra-high performance liquid chromatography tandem mass spectrometry.

Liposome encapsulating cytarabine (CYT) and daunorubicin (DNR) is applied for treating Acute Myeloid Leukemia (AML) patients. To evaluate and compare relationship between the pharmacokinetics of free drug (drug which is not entrapped in liposomes) and liposome-encapsulated drug and the toxicity/efficacy, it is crucial to have trustworthy methods for separating the free and the encapsulated of the drug. In this study, methods were developed and validated to isolate and measure the free DNR/CYT (F-DNR/CYT), the encapsulated DNR/CYT (E-DNR/CYT) and the total DNR/CYT (T-DNR/CYT) in rat plasma. The methods involved solid-phase extraction (SPE) using reverse adsorbents for separating the F-DNR and E-DNR, SPE using cation exchange adsorbents for separating the E-CYT, ultrafiltration for isolating the F-CYT and protein precipitation (PPT) for releasing the T-DNR and T-CYT totally from the liposomal forms. The analytes were subsequently quantified on ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) individually with multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The calibration curves showed good linear relationships over the concentration range of 0.22-44 µg/mL for E-DNR and T-DNR, 2-1000 ng/mL for F-DNR, 0.5-100 µg/mL for E-CYT and T-CYT, 4-2000 ng/mL for F-CYT respectively. For all the analytes, the within-and between-run precisions were less than13.6% and the accuracies (in terms of RE%) were within -12.5%. Besides, extraction recovery, matrix effect, dilution integrity and stability were also assessed. The methods were successfully applied to investigate the pharmacokinetics in Sprague-Dawley rats following i.v. administration liposomal formulation.

Liposome-based immunostrip for the rapid detection of Salmonella.

Salmonellae are ubiquitous human pathogens, which pose a danger to the elderly and children. Due to the increased number of outbreaks of human illness associated with the consumption of contaminated products in the USA and many other countries, there is an urgent need to develop rapid assays to detect common food-borne pathogens. This study demonstrates the feasibility of using a detectable label comprising methyl blue (MB), a visible dye, entrapped inside liposomes. Immunoliposomes tagged with anti-Salmonella common structural antigens (CSA) antibody encapsulating MB dye were prepared and used as the signal amplifier for the development of a field-portable colorimetric immunoassay to detect Salmonellae. Tapping mode atomic force microscopy (TMAFM), a scanning probe technique, was utilized to demonstrate the presence of anti-Salmonella antibody at the thus-prepared liposome. A plastic-backed nitrocellulose strip with two immobilized zones formed the basis of a sandwich assay. The first zone was the antigen capture zone (AC zone), used in a sandwich (noncompetitive) assay format; the other was the biotin capture zone (BC zone), used as a quality control index for the strip assay. During the capillary migration of the wicking reagent containing 80 µL of immunoliposomes and 40 µL of the test sample (heat-killed S. typhimurium), sample pathogens with surface-bound immunoliposomes were captured at the AC zone, while the unbound immunoliposomes continued to migrate and bind to the anti-biotin antibodies coated on the BC zone. The color density of the AC zone was directly proportional to the number of Salmonella typhimurium in the test sample. The detection limit of the current assay with heat-killed Salmonella typhimurium was 1,680 cells. The cross-reactivity of the proposed immunoassay was also investigated, and pathogens including E. coli O157:H7 and Listeria genus specific caused no interference with the detection of Salmonella typhimurium.

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis.

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.

Preparation and characterization of nano-hydroxyapatite/poly(vinyl alcohol) composite membranes for guided bone regeneration.

In this study, nano-hydroxyapatite/poly(vinyl alcohol) (n-HA/PVA) composite membranes were prepared by solvent casting and evaporation method. The morphology, mechanical properties, water absorption behavior, contact angle measurement and biocompatibility of these membranes were examined by SEM, FTIR, XRD, MTT assay and etc. The results demonstrate that the surface of composite membranes is suitable for the adhesion and proliferation of osteogenic cells, and that n-HA and PVA are in uniform distribution when the content of n-HA is less than 20 wt%. Tests of swelling behavior and water contact angle show that the incorporation of n-HA into PVA matrix significantly reduces its hydrophilicity. Mechanical tests reveal that the addition of n-HA nanoparticles reduces tensile strength and elongation rate but increases Young's modulus of composite membranes. Cell attachment test and MTT assay prove that n-HA/PVA composite membranes have good biocompatibility. Therefore, the n-HA/PVA composite membranes possess potential application for guided bone regeneration (GBR).

Preparation of magnetic microspheres based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymers by modified solvent diffusion method.

Magnetic microspheres have promising application in biomedical field. In this paper, biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) triblock copolymers were synthesized by ring-opening polymerization method. Through adjusting the epsilon-CL/PEG weight ratio in feed, PCEC copolymers with different block ratio were obtained. A novel modified solvent diffusion method was described to prepare magnetic PCEC composite microspheres containing magnetite nanoparticles. The particle size of microsphere decreased with increase in the PEG/PCL block ratio. The obtained microspheres could response to external magnetic field. This study described a novel method to prepare magnetic microspheres. The obtained magnetic polymeric microspheres might have potential application in drug delivery system or disease diagnosis field.

Injectable biodegradable thermosensitive hydrogel composite for orthopedic tissue engineering. 1. Preparation and characterization of nanohydroxyapatite/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) hydrogel nanocomposites.

In this study, we synthesized a biodegradable triblock copolymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) by ring-opening copolymerization, and nanohydroxyapatite (n-HA) powder was prepared by a hydrothermal precipitation method. The obtained n-HA was incorporated into the PECE matrix to prepare injectable thermosensitive hydrogel nanocomposites. (1)H NMR, FT-IR, XRD, DSC, and TEM were used to investigate the properties of PECE copolymer and n-HA/PECE nanocomposites. The rheological measurements for n-HA/PECE nanocomposites revealed that the gelation temperature was approximately 36 degrees C. The sol-gel-sol transition behavior and phase transition diagrams were recorded through a test tube inverting method. The results showed that n-HA/PECE nanocomposites still had thermoresponsivity like that of PECE thermosensitive hydrogel. The morphology of the nanocomposites was observed by SEM; the results showed that the nanocomposites had a 3D network structure. In addition, the effects of n-HA contents on the properties of n-HA/PECE nanocomposites are also discussed in the paper. From the results, n-HA/PECE hydrogel is believed to be promising for injectable orthopedic tissue engineering due to its good thermosensitivity and injectability.

Self-assembled honokiol-loaded micelles based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer.

Self-assembled polymeric micelles are widely applied in drug delivery system (DDS). In this study, honokiol (HK) loaded micelles were prepared from biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) copolymers. Micelles were prepared by self-assembly of triblock copolymer PCEC in distilled water triggered by its amphiphilic character without any organic solvent. Drug loading and encapsulation efficiency were determined by adjusting the weight ratio of HK and PCEC. The particle size and zeta potential distribution of obtained micelles were determined using Malvern laser particle sizer, and spherical geometry were observed on atomic force microscope (AFM). Otherwise, the thermo-sensitivity of honokiol-loaded micelles was monitored. And the cytotoxicity results of drug loaded micelles showed that the encapsulated honokiol remained potent antitumor effect. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free honokiol and much slower and sustained release of HK-loaded micelles. These results suggested that we have successfully prepared honokiol-loaded micelles in an improved method which is safer and more efficient. The prepared micelles might be potential carriers for honokiol delivery in cancer chemotherapy.

Poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) nanoparticles for honokiol delivery in vitro.

In this article, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles were successfully prepared for honokiol delivery in vitro. Blank or honokiol loaded PCL-PEG-PCL nanoparticles were prepared in moderate condition by solvent diffusion method without using any surfactants. The prepared blank PCL-PEG-PCL nanoparticles are mono-dispersed and smaller than 200 nm. The particle size increased with increase in polymer concentration and oil-water (O/W) ratio. The prepared PCL-PEG-PCL nanoparticles (40 mg/mL, ca. 106 nm) did not induce hemolysis in vitro. And the 50% inhibiting concentration (IC50) of it (48 h) on HEK293 cells was higher than 5 mg/mL. Honokiol could be efficiently loaded into PCL-PEG-PCL nanoparticles and released from these nanoparticles in an extended period in vitro. After honokiol (HK) was entrapped into PCL-PEG-PCL nanoparticles, the particle size increased with the increase in HK/PCEC mass ratio in feed, and the encapsulated honokiol retained potent anticancer activity in vitro. The PCL-PEG-PCL nanoparticle was suitable for honokiol delivery, and such honokiol loaded PCL-PEG-PCL nanoparticle was a novel honokiol formulation.