Inhalable FN-binding liposomes or liposome-exosome hybrid bionic vesicles encapsulated microparticles for enhanced pulmonary fibrosis therapy.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.

Efficient pulmonary fibrosis therapy via regulating macrophage polarization using respirable cryptotanshinone-loaded liposomal microparticles.

Lung inflammation and fibrogenesis are the two main characteristics during the development of pulmonary fibrosis (PF), which are particularly associated with pulmonary macrophages. In this context, whether cryptotanshinone (CTS) could alleviate PF through regulating macrophage polarization were preliminarily demonstrated in vitro. Then the time course of PF and its relationship with macrophage polarization was determined in BLM-induced mice based on cytokine levels in bronchoalveolar lavage fluid (BALF), lung histopathology, flow cytometric analysis, mRNA and protein expression. CTS was loaded into macrophage-targeted and responsively released mannose-modified liposomes (Man-lipo), and the liposomes were then embedded into mannitol microparticles (M-MPs) using spray drying to achieve efficient pulmonary delivery. Afterwards, how CTS regulates macrophage polarization in vivo during different time courses of PF was probed. Furthermore, the molecular mechanisms of CTS against PF by regulating macrophage polarization were elucidated in vivo and in vitro. The full-course therapy group could achieve comparable therapeutic effects compared with the positive control drug PFD group. CTS can alleviate PF through regulating macrophage polarization, mainly by inhibiting NLRP3/TGF-ß1 pathway during the inflammation course and modulating MMP-9/TIMP-1 balance during the fibrosis development course, providing new insights into chronic PF treatment.

Synergistic enhancement of modified sericite on rheological and foaming properties of poly (lactic acid).

Due to low melt strength and slow crystallization rate, poly (lactic acid) (PLA) foam materials are still not satisfactory. In order to improve the foaming performance of PLA, sericite (GA) was selected as the filler and modified by 3-Aminopropyltriethoxysilane (KH-550). Through melt blending with PLA, azodicarbonamide (ADC) foaming agent was selected for molding foaming, and PLA/GA composite foam was prepared. The addition of GA not only acts as a nucleating agent to improve the crystallization performance of the blend, but also improves its complex viscosity and storage modulus, and enhances its melt strength, so that the compressive strength and impact strength of the prepared composite foam are increased by 265.5 % and 224.0 %, respectively. Compared with PE foam, PLA/GA composite foam showed excellent thermal insulation performance through thermal infrared imaging test. Based on its mechanical and thermal insulation properties, this sample provides new materials for the field of wall insulation and foam packaging. This study provides an effective way to improve the melt strength and workability of PLA.

In vitro evaluation of polymeric micelles based on hydrophobically-modified sulfated chitosan as a carrier of doxorubicin.

Four types of doxorubicin (DOX)-loaded polymeric micelles based on hydrophobically-modified sulfated chitosan (SCTS) were prepared. The hydrophobic group was composed of glycyrrhetinic acid (GA), cholic acid, stearic acid (SA) or lauric aldehyde. DOX encapsulation depended on several parameters, including the degree of substitution of the sulfate group and the hydrophobic group, and the type of hydrophobic group. Of these micelles, GA-SCTS micelles had the best capability to solubilize DOX. In addition, GA-SCTS micelles had the ability to target HepG(2) cells, and the IC50 for DOX-loaded GA-SCTS micelles was 54.7 ng/mL, which was much lower than that of the other micelles. Further studies on the DOX-loaded GA-SCTS micelles showed that they were stable in salt and protein solutions, in cell culture media, and during long-term storage (6 months). Based on these results, these micelles may be a promising DOX-encapsulated formulation, particularly, GA-SCTS as a potential vehicle for liver-targeted delivery.

Nutritional Status and Sarcopenia in Nursing Home Residents: A Cross-Sectional Study.

OBJECTIVE: This study aimed to assess the nutritional status and sarcopenia in older people living in nursing homes. METHODS: This cross-sectional study enrolled 386 older adults in nursing homes in Hunan Province, China. Assessments included the Mini Nutritional Assessment Short Form for nutrition risk, Dietary Diversity Score for dietary diversity and Mini Mental State Examination for cognitive status. Sociodemographic (e.g., age, sex and educational level), health-related characteristics (e.g., food intake, self-care status and medication), body composition (e.g., body mass index [BMI], protein, body fat mass [BFM], percent body fat [PBF], skeletal muscle index [SMI] and total body water [TBW]) and anthropometric parameters data (e.g., calf circumference [CC], upper arm circumference [UAC], handgrip and gait speed) were also collected. Malnutrition and their associated risk were analyzed by multivariable Poisson regression analysis. RESULTS: In total, 32.4% of participants (n = 125) were at risk of malnutrition and 49.7% (n = 192) suffered from sarcopenia. Nutritional status was positively associated with age (risk ratio [RR] = 1.03), sarcopenia (RR = 1.88), tooth loss affecting food intake (RR = 1.45), low self-care status (RR = 1.82) and moderate/inadequate dietary diversity (RR = 2.04) and negatively associated with one child (RR = 0.27), BMI (RR = 0.82), protein (RR = 0.76), BFM (RR = 0.91), PBF (RR = 0.94), SMI (RR = 0.65), TBW (RR = 0.94), CC (RR = 0.89) and UAC (RR = 0.86). CONCLUSIONS: Age, number of children, sarcopenia, food intake, self-care status, dietary diversity and body composition were associated with malnutrition among nursing home residents. For vulnerable groups, researchers should focus on raising the body composition indicators, such as BMI, protein, BFM, SMI and TBW and measuring CC and UAC for initial screening.

Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier.

Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(γ-benzyl L-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX · HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX · HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.

Rapid and Highly Effective Noninvasive Disinfection by Hybrid Ag/CS@MnO2 Nanosheets Using Near-Infrared Light.

A bacterial infection on the surface of medical apparatus and instruments as well as artificial implants is threatening human health greatly. Antibiotics and traditional bacterial-killing agents, even silver nanoparticles, can induce bacterial resistance during long-term interaction with bacteria. Hence, rapid surface sterilization and prevention of bacterial infection in the long term are urgent for biomedical devices, especially for artificial implant materials. Herein, a hybridized chitosan (CS), silver nanoparticles (AgNPs), and MnO2 nanosheets coating was designed on the surface of titanium plates, which can ensure the implants a rapid and highly effective antibacterial efficacy of 99.00% against Staphylococcus aureus ( S. aureus) and 99.25% against Escherichia coli ( E. coli) within 20 min of 808 nm near-infrared light (NIR) irradiation. The exogenous NIR irradiation can trigger the MnO2 nanosheets to produce enough hyperthermia within 10 min, which can combine with a low concentration of prereleased Ag+ from the coating to achieve superior antimicrobial efficacy through synergistic effects. In contrast, either prereleased Ag ions or a photothermal effect alone can achieve much lower antibacterial efficiency under the same concentration, i.e., 24.00% and 30.01% for the former and 30.00% and 42.54% for the later toward S. aureus and E. coli, respectively. The possible cytotoxicity of coatings could be eliminated owing to the low concentration of AgNPs and chitosan encapsulation. Thus, the novel bifunctional coating Ag/CS@MnO2 can exhibit great potential in deep site disinfection of Ti implants through the synergy of prereleased Ag ions and a photothermal effect within a short time.

Construction of perfluorohexane/IR780@liposome coating on Ti for rapid bacteria killing under permeable near infrared light.

Near infrared (NIR) light induced photodynamic antibacterial therapy (PDAT) is a promising antibacterial technique in rapid in situ disinfection of bacterially infected artificial implants due to its penetration ability into tissues. However, the lower oxygen content in vivo may restrict the yields of reactive oxygen species (ROS), thus reducing the antibacterial efficacy of PADT significantly. Herein, liposome encapsulated photosensitizers (PS), IR780 and perfluorohexane (PFH), have been constructed on the surface of Ti implants via a covalent linkage to overcome this issue. Thanks to the high oxygen capacity of PFH, more ROS can be generated during NIR irradiation regardless of the low content of oxygen in vivo. As a result, in vitro tests demonstrated that 15 minutes of 808 nm near-infrared irradiation could achieve a high antibacterial efficacy of 99.62% and 99.63% on the implant surface against Escherichia coli and Staphylococcus aureus, respectively. By contrast, the PDAT system without PFH modification shows a lower antibacterial efficacy (only 66.54% and 48.04%, respectively). In addition, this enhanced PDAT system also possesses great biocompatibility based on the in vitro and in vivo subcutaneous assays. This surface system makes it possible for rapid bacteria-killing in artificial implants that have been implanted in vivo under local conditions with lower oxygen content.

Influence of polymeric carrier on the disposition and retention of 20(R)-ginsenoside-rg3-loaded swellable microparticles in the lung.

The objective of this study was to investigate the influence of differently charged biocompatible polymers, including chitosan (CS), hyaluronic acid (HA), and hydroxypropyl cellulose (HPC), on the disposition and retention of 20(R)-ginsenoside-rg3 (Rg3)-loaded swellable microparticles in the lung. A high-pressure homogenization method combined with spray drying was used to prepare Rg3-loaded microparticles. In vitro aerodynamic performance of different microparticles was characterized by the Next Generation Impactor (NGI). Retention of the swellable microparticles in the rat lung was investigated using bronchoalveolar lavage fluid method. Influence of drug loading, polymer molecular weight, and polymer charge on the properties of the swellable microparticles was investigated. It was found that drug loading had no significant influence on experimental mass median aerodynamic diameter (MMADe) and fine particle fraction (FPF). Increasing polymer molecular weight caused no remarkable change in MMADe value, but the FPF value decreased with the increase of polymer molecular weight. At the same molecular weight level, polymer structure and charge had no statistical influence on the in vitro aerodynamic properties of the microparticles and lung disposition, but it influenced the swelling and bioadhesion behavior and therefore lung retention profile. Desirable phagocytosis escapement and inhibition of A549 cell proliferation were achieved for the developed swellable microparticles. In conclusion, the lung retention of swellable microparticles can be adjusted by selecting polymeric carriers with different structure and charge.

Insight into glycyrrhetinic acid: the role of the hydroxyl group on liver targeting.

Two kinds of glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles (CTS/PEG-GA NPs) were prepared by an ionic gelation process in which the liver targeting ligand glycyrrhetinic acid (GA) was introduced into the nanoparticles at the C(30)-carboxyl group (CTS/PEG-GA(c) NPs) or the C(3)-hydroxyl group (CTS/PEG-GA(h) NPs). Their characteristics, especially their ability to target the liver, were compared. The results showed that both the CTS/PEG-GA(c) NPs and the CTS/PEG-GA(h) NPs are remarkably targeted to the liver. The accumulation in the liver is 51.3% and 56.5% of the injected dose for the CTS/PEG-GA(c)(4.60%) NPs (the subscript number denotes the GA content as weight percent in nanoparticles) and the CTS/PEG-GA(h)(4.57%) NPs at 3 h after injection, respectively. This is nearly 2.6-2.8 times higher than that obtained with the CTS/PEG NPs. According to our results, there is no significant difference between the CTS/PEG-GA(c) NPs and the CTS/PEG-GA(h) NPs in their ability to target the liver, when they were formed under identical conditions. This indicated that the C(3)-hydroxyl group in GA has little influence on the targeting ability.

Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery.

A liver-targeted drug delivery carrier, composed of chitosan/poly(ethylene glycol)-glycyrrhetinic acid (CTS/PEG-GA) nanoparticles, was prepared by an ionic gelation process, in which glycyrrhetinic acid (GA) acted as the targeting ligand. The formation and characterization of these nanoparticles were confirmed by FT-IR, dynamic light scattering (DLS) and zeta potential measurements. The biodistribution of the nanoparticles was assessed by single-photon emission computed tomography (SPECT), and the cellular uptake was evaluated using human hepatic carcinoma cells (QGY-7703 cells). The anti-neoplastic effect of the doxorubicin.HCl-loaded nanoparticles (DOX-loaded nanoparticles) was also investigated in vitro and in vivo. The results showed that the CTS/PEG-GA nanoparticles were remarkably targeted to the liver, and keep at a high level during the experiment. The accumulation in the liver was 51.3% at 3 h after injection; this was nearly 2.6 times that obtained with the CTS/PEG nanoparticles. The DOX-loaded nanoparticles were greatly cytotoxic to QGY-7703 cells, and the IC(50) (50% inhibitory concentration) for the free doxorubicin.HCl (DOX.HCl) and the DOX-loaded CTS/PEG-GA nanoparticles were 47 and 79 ng/mL, respectively. Moreover, the DOX-loaded CTS/PEG-GA nanoparticles could effectively inhibit tumor growth in H22 cell-bearing mice.