Explore the vast range of titles available.

Aliphatic polyesters are the most common type of biodegradable synthetic polymer used in many pharmaceutical applications nowadays. This report describes the ring-opening polymerization (ROP) of l-lactide (L-LA), ε-caprolactone (CL) and glycolide (Gly) in the presence of a simple, inexpensive and convenient PEG200-BiOct3 catalytic system. The chemical structures of the obtained copolymers were characterized by 1H- or 13C-NMR. GPC was used to estimate the average molecular weight of the resulting polyesters, whereas TGA and DSC were employed to determine the thermal properties of polymeric products. The effects of temperature, reaction time, and catalyst content on the polymerization process were investigated. Importantly, the obtained polyesters were not cyto- or genotoxic, which is significant in terms of the potential for medical applications (e.g., for drug delivery systems). As a result of transesterification, the copolymers obtained had a random distribution of comonomer units along the polymer chain. The thermal analysis indicated an amorphous nature of poly(l-lactide-co-ε-caprolactone) (PLACL) and a low degree of crystallinity of poly(ε-caprolactone-co-glycolide) (PCLGA, Xc = 15.1%), in accordance with the microstructures with random distributions and short sequences of comonomer units (l = 1.02–2.82). Significant differences in reactivity were observed among comonomers, confirming preferential ring opening of L-LA during the copolymerization process.

Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss. We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly( -caprolactone)- -PEG- -poly( -caprolactone) 'flower-like polymeric micelles. The chemical stability of RIF was evaluated under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia. Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH. Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration. Original submitted 6 April 2013; Revised submitted 7 August 2013

Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL-PEG-PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1 ± 2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 μg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58 ± 0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67 ± 0.78; P<0.001, Mann-Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL-PEG-PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions.

Acne is the over growth of the commensal bacteria Propionibacterium acnes (P. acnes) on human skin. Lauric acid (LA) has been investigated as an effective candidate to suppress the activity of P. acnes. Although LA is nearly insoluble in water, dimethyl sulfoxide (DMSO) has been reported to effectively solubilize LA. However, the toxicity of DMSO can limit the use of LA on the skin. In this study, LA-loaded poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) micelles (PCL-PEG-PCL) were developed to improve the bactericidal effect of free LA on P. acnes. The block copolymers mPEG-PCL and PCL-PEG-PCL with different molecular weights were synthesized and characterized using 1H Nuclear Magnetic Resonance spectroscopy (1H NMR), Fourier-transform infrared spectroscopy (FT-IR), Gel Permeation Chromatography (GPC), and Differential Scanning Calorimetry (DSC). In the presence of LA, mPEG-PCL diblock copolymers did not self-assemble into nano-sized micelles. On the contrary, the average particle sizes of the PCL-PEG-PCL micelles ranged from 50–198 nm for blank micelles and 27–89 nm for LA-loaded micelles. The drug loading content increased as the molecular weight of PCL-PEG-PCL polymer increased. Additionally, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of free LA were 20 and 80 μg/mL, respectively. The MICs and MBCs of the micelles decreased to 10 and 40 μg/mL, respectively. This study demonstrated that the LA-loaded micelles are a potential treatment for acne.

To develop a suitable formulation of curcumin-encapsulated methoxy poly(ethylene glycol) (MePEG)/poly- -caprolactone (PCL) diblock copolymeric micelle by varying the copolymer ratio, for achieving small sized micelles with high encapsulation of curcumin. To evaluate the micelle s aqueous solubility and stability, efficiency of cellular uptake, cell cytotoxicity and ability to induce apoptosis on pancreatic cell lines. Amphiphilic diblock copolymers (composed of MePEG and PCL) were used in various ratios for the preparation of curcumin-encapsulated micelles using a modified dialysis method. Physicochemical characterization of the formulation included size and surface charge measurement, transmission electron microscopy characterization, spectroscopic analysis, stability and release kinetics studies. The anticancer efficacy of the curcumin-encapsulated micelle formulation was compared with unmodified curcumin in terms of cellular uptake, cell cytotoxicity and apoptosis of pancreatic cell lines MIA PaCa-2 and PANC-1. Physiochemical characterization of the formulations revealed that curcumin was efficiently encapsulated in all formulation of MePEG/PCL micelles; however, a 40:60 MePEG:PCL ratio micelle was chosen for experimental studies owing to its high encapsulation (∼60%) with size (∼110 nm) and negative potential (∼-16 mV). Curcumin-encapsulated micelles increased the bioavailability of curcumin due to enhanced uptake (2.95 times more compared with unmodified) with comparative cytotoxic activity (by induction of apoptosis) compared with unmodified curcumin at equimolar concentrations. IC values for unmodified curcumin and curcumin micelles were found to be 24.75 µM and 22.8 µM for PANC-1 and 14.96 µM and 13.85 µM for MIA PaCa-2, respectively. Together the results clearly indicate the promise of a micellar system for efficient solubilization, stabilization and controlled delivery of the hydrophobic drug curcumin for cancer therapy.

To evaluate the efficacy of electrically conductive, biocompatible composite scaffolds in modulating the cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs). Electrospun scaffolds of poly( -caprolactone) with or without carbon nanotubes were developed to promote the cardiac differentiation of hMSCs. Results indicate that hMSC differentiation can be enhanced by either culturing in electrically conductive, carbon nanotube-containing composite scaffolds without electrical stimulation in the presence of 5-azacytidine, or extrinsic electrical stimulation in nonconductive poly( -caprolactone) scaffolds without carbon nanotube and azacytidine. This study suggests a first step towards improving hMSC cardiomyogenic differentiation for local delivery into the infarcted myocardium. Original submitted 23 July 2012; Revised submitted 31 October 2012; Published online 27 March 2013

Molecularly imprinted polymers (MIP) are materials capable of recognizing specific molecules, usually through non-covalent bonds. In this work, gallic acid (GA) was selected as the imprinting molecule, and MIP for GA (MIP-GA) was synthesized by bulk polymerization. X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) confirmed the MIP-GA recognition property. Poly(caprolactone) mat containing MIP-GA particles (MIM-GA) was produced by electrospinning, which was morphologically characterized by Scanning electron microscopy (SEM). Functionalized MIM-GA was obtained by washes sequence in methanol for the GA removal from MIM-GA. The GA removal was confirmed by High-performance liquid chromatography (HPLC) with UV-Vis detection at 214 and 268 nm. The functionalized MIM-GA immersed in GA methanolic solution with a concentration of 1.0 mM extracted 96±1.5% of GA at t = 150 minutes. The vibrational modes obtained from FT-IR spectra confirmed the chemical composition of MIM-GA and its functionalization through of band at 770 cm-1. The contact angle measurements were 134.0±1.0° for electrospun MIM-GA and 125.0±1.2° for functionalized MIM-GA. The decrease was due to the absence of GA after the functionalization process. The produced MIM-GA by electrospinning acquired the recognition property of the GA imprinted polymer synthesized, which can be used for the specific detection, extraction, and purification of this important natural polyphenol.

In this study, a novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)‐poly(lactide) (mPEG‐PLA) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) (mPEG‐PCL), used as a novel nanocarrier to encapsulate gambogenic acid (GNA). GNA‐loaded mixed polymeric micelles (GNA‐MMs) was prepared by cosolvent evaporation method. The mean average size of GNA‐MMs was (83.23 ± 1.06) nm (n = 3) and entrapment efficiency (EE%) of GNA‐MMs was (90.18 ± 2.59) % (n = 3) as well as (12.36 ± 0.64) % (n = 3) for drug loading (DL%). Transmission electron microscopy revealed that the GNA‐MMs were spherical with “core‐shell” structures. Compared with free GNA solution, in vitro release of GNA from GNA‐MMs showed a two‐phase sustained release profile: an initial relatively fast phase and followed by a slower release phase. Pharmacokinetic results also indicated that the GNA‐MMs have longer systemic circulation time and slower plasma elimination rate than free GNA solution. Moreover, the in vitro cytotoxicity assay showed that the IC50 values on HepG2 cells for GNA‐MMs and free GNA were (5.67 ± 0.02) μM and (9.02 ± 0.03) μM, respectively. In addition, GNA‐MMs significantly increased the HepG2 cellular apoptosis in a concentration‐dependent manner. In conclusion, the results showed that mPEG‐PLA/mPEG‐PCL mixed micelles may serve as an ideal drug delivery system for GNA to prolong drug circulation time in body, enhance bioavailability and retained its potent antitumor effect.

This study evaluated the potential of using poly(lactic acid)/poly(s-caprolactone) (PLA/PCL) blends for fused filament fabrication (FFF) and assembly with pure PLA for biomedical applications. PLA/PCL binary blends were meltblended in a twin-screw extruder at different ratios (20/80 to 80/20) and then formed into filaments with a calibrated diameter for FFF. The microstructure, surface properties, and rheological and mechanical behaviors of the blends were assessed. The blends were immiscible but showed signs of adhesion between the phases. It was determined that the fibrillar morphology of inclusions for PLA/PCL ratios higher than 30/70 proved to be driven by the manufacturing process. The tensile mechanical behaviors of printed and injected samples were similar, and their Young's modulus was simulated using Halpin-Tsai and Mori Tanaka models based on the sample microstructure. The ductility of the blends was strongly driven by the behavior of its majority phase. Finally, specific samples were designed to characterize the tensile strength between PLA and its blends by entangling layers of both materials. The strength of the assembly was found to be dependent on the phase that was continuous and was governed by the strength and the viscosity of the blend.

Jingyi Hong,1,* Yanhong Li,1,2,* Yijing Li,1 Yao Xiao,1,2 Haixue Kuang,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 2School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China *These authors contributed equally tothis work Abstract: Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps) were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol)2000-poly (ε-caprolactone)2000 (mPEG2000-PCL2000) as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2nm, a zeta potential of -20.17mV, and a high drug payload of 73.68%. ACGs-NSps were quite stable in various physiological solutions, and they exhibited sustained drug release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against 4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation after labeling with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, a noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor-bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy than the traditional dosage form (oil solution) even at 1/10 of the dose (74.83% vs 45.53%, P<0.05), demonstrating that NSp was a good dosage form for ACGs to treat cancer. Keywords: annonaceous acetogenins, mPEG2000-PCL2000, near-infrared fluorescence, biodistribution, antitumor efficacy