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Either cardiovascular or peripheral vascular diseases have become the major cause of morbidity and mortality worldwide. Recently, growth factors therapeutics, whatever administrated in form of exogenous growth factors or their relevant genes have been discovered to be an effective strategy for the prevention and therapy of vascular diseases, because of their promoting angiogenesis. Besides, as an alternative, stem cell-based therapy has been also developed in view of their paracrine-mediated effect or ability of differentiation toward angiogenesis-related cells under assistance of growth factors. Despite of being specific and potent, no matter growth factors or stem cells-based therapy, their full clinical transformation is limited from bench to bedside. In this review, the potential choices of therapeutic modes based on types of different growth factors or stem cells were firstly summarized for vascular diseases. The confronted various challenges such as lack of non-invasive delivery method, the physiochemical challenge, the short half-life time, and poor cell survival, were carefully analyzed for these therapeutic modes. Various strategies to overcome these limitations are put forward from the perspective of drug delivery. The expertised design of a suitable delivery form will undoubtedly provide valuable insight into their clinical application in the regenerative medicine., (Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Though many agents have therapeutic potentials for brain diseases, few have been used in clinical environments because of the brain barriers. As an effective interventional technique, ultrasound (US) could be a potentially feasible approach to disrupt the blood-brain barrier (BBB) and deliver therapeutic agents into the brain., Areas Covered: This article reviews up-to-date ultrasound-mediated strategies in opening the brain barriers for drug brain delivery. The mechanisms and problems of these approaches are discussed, as well as the challenges and potentials associated with the ultrasound-mediated strategies that are currently available or under development., Expert Opinion: Despite recent successes in opening the blood brain barrier (BBB) via microbubble-enhanced focused ultrasound, the exact mechanisms of how the barrier is disrupted, remains unknown. A complete understanding of the mechanisms involved in the ultrasound-mediated disruption of the BBB and improving the efficiency of drug delivery to targeted brain regions can greatly facilitate the successful development and translation of the technology.

Polymeric nanoparticles are widely used as targeted carriers for biomacromolecules. In this paper, modified gelatin nanoparticles were prepared and their feasibility as insulin pulmonary administration system was investigated. D: ,L: -glyceraldehyde and poloxamer 188 were used for gelatin nanoparticle preparation. Novel water-in-water emulsion technique was used to prepare insulin-loaded nanoparticles. Morphological examination of insulin-loaded nanoparticles was carried out using scanning electron microscopy (SEM). Intratracheal instillation of insulin-loaded nanoparticles was performed to evaluate animal hypoglycemic effect. With fluorescence labeling of insulin, alveolar deposition and absorption of insulin-loaded nanoparticles were investigated. Histological changes in the lung were also observed to evaluate the safety. From the micromorphology observation, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 showed smooth and uniform surface, with average particle size 250 nm and Zeta potential -21.1 mV. From animal experiment, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability. Proved by alveolar deposition result, FITC-insulin-loaded nanoparticle group was characterized by an acute and rapid hypoglycemic effect. In addition, nanoparticles could guarantee the safety of lung by reducing insulin deposition in lung. A transient weak inflammatory response was observed at 1 day after administration. With good physical characterization, high bioavailability, fast and stable hypoglycemic effect, insulin-loaded nanoparticles might be developed as a novel insulin pulmonary system for diabetes therapy.

Objective: An in vivo study on enhancing antitumor effect of intravenous epirubicin hydrochloride (EPI) by acoustic cavitation in situ combined with phospholipid-based microbubbles (PMB) was reported., Methods: Five-week-old male nude mice were used, and HCT-116 cells were s.c. (subcutaneous injection) inoculated in axilla of these mice. Five groups were designed and five consecutive treatments were applied to investigate the tumor growth, body weight growth, and normal organ growth., Results: Inhibition effects on tumor growth were observed in all groups treated by EPI. However, the potency of tumor growth retardation caused by EPI depended on the application of PMB and US in situ. An effective retardation on tumor growth and improved mice survival status were observed when intravenous EPI combined with sonicated PMB in situ. Short-term lingering sensitive period for chemotherapeutic drugs after acoustic cavitation was also observed in experiment under asynchronous administration of EPI and sonicated PMB., Conclusion: Intravenous EPI combined with PMB-mediated cavitation in situ might provide a potential application for US-mediated chemotherapy.

The objective of this study was to investigate the factors for enhancing the susceptibility of cancer cells to chemotherapeutic drug by ultrasound microbubbles. Ultrasound (US) combined with phospholipid-based microbubbles (MB) was used to enhance the susceptibility of colon cancer cell line SWD-620 to anticancer drugs Topotecan hydrochloride (TOP). Experiments were designed to investigate the influence of main factors on cell viability and cell inhibition, such as US intensity, MB concentration, drug combination with MB, asynchronous action between US triggered cavitation and drug entering cell, MB particle size. US exposure for 10 sec with US probe power at 0.6 W/cm(2) had satisfied cell viability. Treated with US combined with 15% MB, cell viability maintained more than 85% and cell inhibition 86.16%. Under optimal US combined with MB, TOP showed much higher cell inhibition than that of only TOP group. Cell inhibition under short delayed time (<2 h) for TOP addition did not show obvious difference. In terms of MB particle size, the order of cell inhibition was: Mixture > Micron bubble part > Nanometer bubble part. US combined with MB can enhance the susceptibility of cancer cells to chemotherapeutic drug, which may provide a potential method for US-mediated tumor chemotherapy.

This work was to compare the encapsulation efficiency and ultrasound-triggered release for protein between microbubbles and liposomes. Bovine serum albumin (BSA) was used as a model. Final ratios between BSA and HPC in microbubbles and liposomes were 1:5, 1:7 and 1:10, respectively. Morphologic characteristics and contrast enhancement of loaded microbubbles and liposomes were measured. Encapsulation efficiency and ultrasound-stimulated release profile were detected. The mean size of loaded microbubbles and liposomes was 3.4 microm and 1.7 microm, respectively. Encapsulation efficiency of microbubbles had an inverse relationship with the ratio between BSA and HPC, while loaded liposomes remained nearly unchanged in the designed range of the ratio between BSA and HPC. Microbubbles resulted in significant enhancement of CnTi images. After ultrasound, more than 90% of the entrapped BSA was released from microbubbles, but less than 5% of BSA released from liposomes. Microbubbles are a promising delivery system for proteins.

Silk was easily dyed in traditional textile industry because of its strong affinity to many colorants. Herein, the biocompatible silk fibroin was firstly extracted from Bombyx mori silkworm cocoons. And SF nanoparticles (SFNPs) were prepared for dyeing indocyanine green (ICG) and construct a therapeutic nano-platform (ICG-SFNPs) for photo-thermal therapy of glioblastoma. ICG was easily encapsulated into SFNPs with a very high encapsulation efficiency reaching to 97.7 ± 1.1%. ICG-SFNPs exhibited a spherical morphology with a mean particle size of 209.4 ± 1.4 nm and a negative zeta potential of −31.9 mV, exhibiting a good stability in physiological medium. Moreover, ICG-SFNPs showed a slow release profile of ICG in vitro, and only 24.51 ± 2.27% of the encapsulated ICG was released even at 72 h. Meanwhile, ICG-SFNPs exhibited a more stable photo-thermal effect than free ICG after exposure to near-infrared irradiation. The temperature of ICG-SFNPs rapidly increased by 33.9 °C within 10 min and maintained for a longer time. ICG-SFNPs were also easily internalized with C6 tumor cells in vitro, and a strong red fluorescence of ICG was observed in cytoplasm for cellular imaging. In vivo imaging showed that ICG-SFNPs were effectively accumulated inside tumor site of C6 glioma-bearing Xenograft nude mice through vein injection. Moreover, the temperature of tumor site was rapidly rising up to kill tumor cells after local NIR irradiation. After treatment, its growth was completely suppressed with the relative tumor volume of 0.55 ± 033 while free ICG of 33.72 ± 1.90. Overall, ICG-SFNPs may be an effective therapeutic means for intraoperative phototherapy and imaging. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles with solid matrix have been given increasing attention due to their biodegradable status and ability to entrap a variety of biologically active compounds. In this study, new phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor (bFGF) were developed to target the brain via nasal administration. Treatment effects were assessed by quantifying rotational behavior, monoamine neurotransmitter levels and tyrosine hydroxylase expression in 6-hydroxydopamine induced hemiparkinsonian rats. The gelatin nanostructured lipid carriers (GNLs) were prepared by a water-in-water emulsion method and then freeze-dried. The GNLs possessed better profile than gelatin nanoparticles (GNs), with particle size 143±1.14nm and Zeta potential −38.2±1.2mV. The intranasal GNLs efficiently enriched exogenous bFGF in olfactory bulb and striatum without adverse impact on the integrity of nasal mucosa and showed obvious therapeutic effects on hemiparkinsonian rats. Thus, GNLs are attractive carriers for nose-to-brain drug delivery, especially for unstable macromolecular drugs such as bFGF. From the Clinical Editor: This team of authors reports the development of phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor to target the brain via intranasal administration. A rat model of hemiparkinsonism was applied demonstrating a good safety profile and an obvious therapeutic effect. [ABSTRACT FROM AUTHOR]

Ultrasound (US)-mediated cavitation of microbubbles has evolved into a new tool for organ-specific gene and drug delivery. This paper was to investigate the feasibility of acidic fibroblast growth factor (aFGF) intravenous delivery to the ischemic myocardium of rats by ultrasonic microbubbles modified with heparin. Heparin modified microbubbles (HMB) were prepared by the freeze-dried method. Acute myocardial infarction (AMI) model was established and the cardio protective effect of the aFGF combing with HMB (aFGF-HMB) under US-mediated cavitation technique was investigated. aFGF-HMB combined with US-mediated cavitation technique was examined by ECG. Ejection fraction (EF), fractional shortening (FS) and left ventricular diastolic diameter (LVDd) were measured to monitor the improvement of global myocardial contractile function. Myocardial tissue was stained with hematoxylin and eosine (HE) to evaluate the elaborate general morphology of the ischemic myocardium. From morphologic observation and echocardiography in rat heart, aFGF-HMB had suitable size distribution, physical stability and good acoustic resonance function. From AMI rat experiments, aFGF-HMB under US-mediated cavitation technique exerted aFGF cardio protective effect in ischemic myocardium. From histological evaluation, US-mediated cavitation of aFGF-HMB showed improvement of myocardial ischemia. With the visual imaging and US-triggered drug release advantages, US-mediated cavitation of aFGF-HMB might be developed as a novel technique for targeting delivery of aFGF into ischemic myocardium. [ABSTRACT FROM AUTHOR]

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes-propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4 ± 89.2 nm), high deformability (Elasticity index == 48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. Aim: In this study, a new heparin–poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy (1H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP–poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. Results: From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5°C, whereas that of the same concentration of poloxamer 188 was 37.3°C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. Conclusion: Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy. [ABSTRACT FROM AUTHOR]