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1.
Fish Shellfish Immunol ; 147: 109460, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38382690

ABSTRACT

Polyethylene microplastics (PE-MPs) has become a global concern due to their widespread distribution and hazardous properties in aquatic habitats. In this study, the accumulation effect of PE-MPs in the intestine of large-scale loach (Paramisgurnus dabryanus) was explored by adding different concentrations of PE-MPs to the water, the destination of PE-MPs after breaking the intestinal barrier and the effects caused. The collected data showed that PE-MPs accumulation for 21d altered the histomorphology and antioxidant enzyme activity of the intestine, induced dysbiosis of the intestinal flora. 10 mg/L of PE-MPs induced a significant increase in the transcript levels of intestinal immunity factors in loach after 21d of exposure. Moreover, the levels of diamine oxidase (DAO) and d-lactic acid (D-Lac) in the gut and serum of loach were significantly increased after exposure to PE-MPs at all concentrations (1, 5, 10 mg/L). Subsequently, the presence of PE-MPs was detected in the blood, suggesting that the disruption of the intestinal multilayer barrier allowed PE-MPs to spill into the circulation. The accumulation of PE-MPs (1,5,10 mg/L) in the blood led to massive apoptosis and necrosis of blood cells and activated phagocytosis in response to PE-MPs invasion. To alleviate the damage, this study further exposure the effect of probiotics on PE-MPs treated loach by adding Leuconostoc mesenteroides DH (109 CFU/g) to the feed. The results showed that DH significantly increased the intestinal index and reduced the levels of DAO and D-Lac. To investigate the reason, we followed the PE-MPs in the intestine and blood of the loach and found that the number of PE-MPs particles was significantly reduced in the probiotic group, while the PE-MPs content in the feces was elevated. Thus, we concluded that DH reducing the accumulation of PE-MPs in the intestinal by increases fecal PE-MPs, which in turn mitigates the damage to the intestinal barrier caused by PE-MPs, and reduces the amount of PE-MPs in the blood. This work offers a robust analysis to understand the mechanisms of damage to the intestinal barrier by MPs and the fate of MPs after escaping the intestinal barrier and provide a new perspective on the application of probiotics in mitigating PE-MPs toxicity.


Subject(s)
Cypriniformes , Leuconostoc mesenteroides , Animals , Polyethylene , Microplastics , Plastics , Antioxidants , Intestines , Blood Cells , Immunity
2.
Sleep Breath ; 25(3): 1543-1552, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33415656

ABSTRACT

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may affect cerebrovascular reactivity (CVR), representing cerebrovascular endothelial function, through complex cerebral functional changes. This study aimed to evaluate the change of CVR after 1-month and 6-month mandibular advancement device (MAD) treatment of patients with carotid atherosclerosis (CAS) combined with OSAHS. METHODS: Patients with carotid atherosclerosis combined with OSAHS who voluntarily accepted Silensor-IL MAD therapy were prospectively enrolled. All patients underwent polysomnographic (PSG) examinations and CVR evaluation by breath-holding test using transcranial Doppler ultrasound at baseline (T0), 1 month (T1), and 6 months (T2) of MAD treatment. RESULTS: Of 46 patients (mean age 54.4 ± 12.4 years, mean body mass index [BMI] 27.5 ± 4.5 kg/m2), 41 patients (responsive group) responded to the 1-month and 6-month treatment of MAD, an effective treatment rate of 89%. The remaining 5 patients (non-responsive group) were younger (47.4 ± 13.5 years) and had a higher BMI (35.8 ± 1.8 kg/m2). The responsive group had an improvement of apnea-hypopnea index (AHI) (events/h) from 33.0 ± 25.0 (T0) to 12.4 ± 10.4 (T1) and 8.7 ± 8.8 (T2), P < 0.001; minimum arterial oxygen saturation (minSpO2) (%) increased from 79.8 ± 9.1 (T0) to 81.8 ± 9.4 (T1) and 85.2 ± 5.4 (T2), P < 0.01; longest apnea (LA) (s) decreased from 46.5 ± 23.1 (T0) to 33.3 ± 22.7 (T1) and 29.4 ± 18.5 (T2), P < 0.001; T90 (%) decreased from 10.3 ± 14.9 (T0) to 6.1 ± 11.8 (T1) and 3.3 ± 7.5 (T2), P < 0.05. Sleep architecture of these patients also improved significantly. The responsive group had a significant increase in left, right, and mean breath-holding index (BHI): left BHI(/s) from 0.52 ± 0.42 (T0) to 0.94 ± 0.56 (T1) and 1.04 ± 0.64 (T2), P < 0.01; right BHI(/s) from 0.60 ± 0.38 (T0) to 1.01 ± 0.58 (T1) and 1.11 ± 0.60 (T2), P < 0.01; mean BHI(/s) from 0.56 ± 0.38 (T0) to 0.97 ± 0.55 (T1) and 1.07 ± 0.59 (T2), P < 0.01), suggesting improved CVR. CONCLUSION: Effective MAD therapy is beneficial for restoring cerebrovascular endothelial function in patients with CAS and OSAHS in a short period (1 month and 6 months). TRIAL REGISTRATION: Clinical trial registration number: NCT03665818. September 11, 2018.


Subject(s)
Carotid Artery Diseases/epidemiology , Cerebrovascular Circulation/physiology , Occlusal Splints , Sleep Apnea, Obstructive/therapy , Adult , Aged , Carotid Artery Diseases/physiopathology , Comorbidity , Female , Humans , Male , Middle Aged , Polysomnography , Prospective Studies , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/physiopathology , Treatment Outcome
3.
BMC Pediatr ; 20(1): 61, 2020 02 10.
Article in English | MEDLINE | ID: mdl-32039717

ABSTRACT

BACKGROUND: Plastic bronchitis (PB) frequently occurs as a serious postoperative complication of the Fontan procedure. The definitive causes of PB are unknown. CASE PRESENTATION: Herein, we report a pediatric case of PB secondary to adenoviral infection. A 4-year-old girl was admitted to the general pediatric ward for cough since 2 weeks and fever since 11 days. Consolidated lesions were noted in the right upper and both lower lung lobes. Extracorporeal membrane oxygenation was performed because the patient's respiratory failure remained unalleviated despite the use of a ventilator. Bronchial dendritic casts were extracted using flexible bronchoscopy, and the patient's breathing improved. Pathological examination of the dendritic cast confirmed the diagnosis of type I PB. The exfoliated cells of sputum and cells from bronchoalveolar lavage fluid were positive for adenoviral antigen. Human adenovirus 7 was detected by next-generation sequencing of the bronchoalveolar lavage fluid. The patient recovered and was discharged 39 days after admission without recurrence of cough or wheezing. CONCLUSIONS: PB due to human adenovirus 7 infection should be considered in children with persistent respiratory failure. Flexible bronchoscopy should be performed early to confirm diagnosis and to remove any airway obstruction.


Subject(s)
Adenoviridae Infections , Anti-Bacterial Agents , Bronchitis , Adenoviridae Infections/complications , Bronchitis/diagnosis , Bronchitis/virology , Bronchoscopy , Child , Child, Preschool , Female , Humans , Plastics , RNA, Ribosomal, 16S
4.
Br J Nutr ; 121(1): 22-29, 2019 01.
Article in English | MEDLINE | ID: mdl-30588901

ABSTRACT

This study investigated the effect of pre-exercise α-lactalbumin ingestion on subsequent endurance exercise performance, muscle pain and mood states. In a two-stage cross-over counterbalance design, eleven male endurance runners (age: 31 (se 2) years, height: 169·5 (se 4·4) cm, weight: 63·6 (se 5·1) kg, V̇O2max: 58·8 (se 6·3) ml/kg per min) consumed two solutions (carbohydrate+α-lactalbumin, CA; carbohydrate+whey protein isolate, CW) 2 h before a self-paced 21-km run. Creatine kinase, IL-6, muscle pain, pressure pain threshold (PPT) and mood states were assessed 2 h before exercise, immediately before exercise (Pre-ex0) and immediately after exercise (Post-ex0). No difference was found in 21-km running performance between two trials (CA v. CW: 115·85 (se 5·20) v. 118·85 (se 5·51) min, P=0·48). Compared with CW, CA led to higher PPT at Pre-ex0 (41·77 (se 2·27) v. 35·56 (se 2·10) N/cm2, P<0·01) and Post-ex0 (38·76 (se 3·23) v. 35·30 (se 3·55) N/cm2, P=0·047). Compared with CW, CA reduced the feeling of fatigue at Post-ex0 (P<0·01); CA also reduced salivary cortisol levels at Post-ex0 (0·72 (se 0·07) v. 0·83 (se 0·13) ng/ml, P<0·01). In conclusion, the ingestion of α-lactalbumin did not improve the 21-km time-trial performance. However, compared with the pre-exercise ingestion of whey protein, that of α-lactalbumin led to superior results during similar levels of endurance exercise: it elevated PPT and reduced the feeling of fatigue and the cortisol levels.


Subject(s)
Affect/drug effects , Athletic Performance/physiology , Exercise/physiology , Lactalbumin/administration & dosage , Physical Endurance/drug effects , Adult , Affect/physiology , Creatine Kinase/blood , Cross-Over Studies , Fatigue , Humans , Hydrocortisone/analysis , Hydrocortisone/blood , Interleukin-6/blood , Male , Myalgia , Oxygen Consumption , Pain Threshold/drug effects , Physical Endurance/physiology , Running/physiology , Saliva/chemistry , Whey Proteins/administration & dosage
5.
J Oral Microbiol ; 16(1): 2361403, 2024.
Article in English | MEDLINE | ID: mdl-38847000

ABSTRACT

Objectives: This research first investigated the effect of mesoporous silica nanoparticles (nMS) carrying chlorhexidine and silver (nMS-nAg-Chx) on periodontitis-related biofilms. This study aimed to investigate (1) the antibacterial activity on Porphyromonas gingivalis (P. gingivalis) biofilm; (2) the suppressing effect on virulence of P. gingivalis biofilm; (3) the regulating effect on periodontitis-related multispecies biofilm. Methods: Silver nanoparticles (nAg) and chlorhexidine (Chx) were co-loaded into nMS to form nMS-nAg-Chx. Inhibitory zone test and minimum inhibitory concentration (MIC) against P. gingivalis were tested. Growth curves, crystal violet (CV) staining, live/dead staining and scanning electron microscopy (SEM) observation were performed. Biofilm virulence was assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Quantitative Real Time-PCR (qPCR) were performed to validate the activity and composition changes of multispecies biofilm (P. gingivalis, Streptococcus gordonii and Streptococcus sanguinis). Results: nMS-nAg-Chx inhibited P. gingivalis biofilm dose-dependently (p<0.05), with MIC of 18.75 µg/mL. There were fewer live bacteria, less biomass and less virulence in nMS-nAg-Chx groups (p<0.05). nMS-nAg-Chx inhibited and modified periodontitis-related biofilms. The proportion of pathogenic bacteria decreased from 16.08 to 1.07% and that of helpful bacteria increased from 82.65 to 94.31% in 25 µg/mL nMS-nAg-Chx group for 72 h. Conclusions: nMS-nAg-Chx inhibited P. gingivalis growth, decreased biofilm virulence and modulated periodontitis-related multispecies biofilms toward healthy tendency. pH-sensitive nMS-nAg-Chx inhibit the pathogens and regulate oral microecology, showing great potential in periodontitis adjunctive therapy.

6.
J Control Release ; 366: 746-760, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38237688

ABSTRACT

Faced with the threat of lung cancer-related deaths worldwide, small interfering RNA (siRNA) can silence tumor related messenger RNA (mRNA) to tackle the issue of drug resistance with enhanced anti-tumor effects. However, how to increase lung tumor targeting and penetration with enhanced gene silencing are the issues to be addressed. Thus, the objective of this study is to explore the feasibility of designing non-viral siRNA vectors for enhanced lung tumor therapy via inhalation. Here, shell-core based polymer-lipid hybrid nanoparticles (HNPs) were prepared via microfluidics by coating PLGA on siRNA-loaded cationic liposomes (Lipoplexes). Transmission electron microscopy and energy dispersive spectroscopy study demonstrated that HNP consists of a PLGA shell and a lipid core. Atomic force microscopy study indicated that the rigidity of HNPs could be well tuned by changing thickness of the PLGA shell. The designed HNPs were muco-inert with increased stability in mucus and BALF, good safety, enhanced mucus penetration and cellular uptake. Crucially, HNP1 with the thinnest PLGA shell exhibited superior transfection efficiency (84.83%) in A549 cells, which was comparable to that of lipoplexes and Lipofectamine 2000, and its tumor permeability was 1.88 times that of lipoplexes in A549-3T3 tumor spheroids. After internalization of the HNPs, not only endosomal escape but also lysosomal exocytosis was observed. The transfection efficiency of HNP1 (39.33%) was 2.26 times that of lipoplexes in A549-3T3 tumor spheroids. Moreover, HNPs exhibited excellent stability during nebulization via soft mist inhaler. In conclusion, our study reveals the great potential of HNP1 in siRNA delivery for lung cancer therapy via inhalation.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/therapy , RNA, Small Interfering , Liposomes , Transfection , A549 Cells
7.
Eur J Pharm Biopharm ; 172: 101-111, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35149189

ABSTRACT

Liposome is the promising nanocarrier for pulmonary drug delivery and surface charge is its basic property. However, there is a lack of knowledge about relationship between the liposomal surface charge and its interaction with biological barriers in the lung. Therefore, the purpose of this research is to elucidate the influence of liposome surface charge on its in vivo fate. Firstly, liposomes with positive, negative and neutral surface charge were constructed and characterized, their compatibility towards pulmonary cells was studied. Then their interaction with different biological barriers in lung, including mucus, trachea, bronchoalveolar lavage fluid (BALF) and alveolar macrophage, were investigated. Their retention behavior in lung and systemic exposure were further explored. It was demonstrated that neutrally and negatively charged liposomes were safer than positively charged ones. In the conducting airway, liposome with positive surface charge could better enhance trachea distribution but only within 2 h. In the respiratory region, both neutrally and negatively charged liposomes presented improved mucus permeability, good stability in BALF containing pulmonary surfactant, decreased macrophage uptake, prolonged lung retention and decreased systemic exposure to other organs, with neutrally charged liposome showing superior performance than the negatively charged ones. While the positively charged liposome was not stable in lung microenvironment with aggregation observed, leading to increased alveolar macrophage uptake, thereby lower pulmonary retention and higher risk of systemic exposure. In conclusion, liposomal surface charge is a tunable formulation factor to modulate the interaction with biological barriers in the lung and thus in vivo fate of inhaled liposomes.


Subject(s)
Liposomes , Lung , Drug Delivery Systems , Macrophages , Macrophages, Alveolar
8.
Photobiomodul Photomed Laser Surg ; 39(12): 789-794, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34797698

ABSTRACT

Objective: This study sought to compare enamel surface morphology and orthodontic bracket re-bonding strength after phosphoric acid- or erbium-doped yttrium aluminum garnet (Er:YAG) laser-mediated re-etching. Methods: A total of 81 extracted premolars were obtained from patients undergoing orthodontic procedures. Conventional etching with 35% phosphoric acid was first used to bond brackets to the enamel surface. Then brackets were de-bonded 1 week later. These samples were then separated randomly into three groups (n = 27 teeth each group) and re-bonded with new brackets after one of the following re-etching manners: Group A-35% phosphoric acid, Group B-Er:YAG laser (200 mJ, 30 Hz), and Group C-Er:YAG laser (250 mJ, 30 Hz). The enamel surface and the interface of enamel and adhesive were then analyzed through scanning electron microscopy. Shear bond strength (SBS) and adhesive remnant index (ARI) were also measured. Results: Samples in Group A exhibited significant residual adhesive at the enamel surface, whereas samples in Groups B and C showed a cleaner surface with more distinct and evenly distributed honeycomb-like structures. Further, samples in Group C displayed a larger average SBS value between the two laser-etching groups, although there were no significant differences in SBS values or ARI scores between the acid and laser re-etching groups (p > 0.05). Conclusions: Er:YAG laser-based enamel re-etching (250 mJ, 30 Hz) produces an uniform honeycomb-like structure and a trend of similar SBS compared with 35% phosphoric acid-mediated re-etching. Er:YAG laser-mediated re-etching seems to be a promising alternative approach for bracket re-bonding.


Subject(s)
Lasers, Solid-State , Orthodontic Brackets , Acid Etching, Dental , Dental Enamel , Humans , Phosphoric Acids , Surface Properties
9.
Carbohydr Polym ; 261: 117873, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-33766360

ABSTRACT

The natural mucus cover has been a major obstacle to prevent enterocyte targeting particles from contact with the receptors. Thus, mucus penetration and intestinal targeting should be designed into one system. Based on the concept that biotin specifically recognizes epithelium receptors, enterocyte targeting muco-inert nanocomplexes were designed. Firstly, biotinylated chitosan (CS-Biotin) copolymers with different degree of substitution were synthesized and characterized. The nanocomplexes between CS-Biotin and insulin were prepared via self-assembly method. Thereafter, the nanocomplexes were fabricated by coating with various molecular weight hyaluronic acid (HA), which improved penetration efficiency in the mucus layer and small intestine in a HA molecular weight dependent manner. In vivo study indicated that hypoglycemic effect of the nanocomplexes was biotin modification degree and HA molecular weight dependent, with HA (200)-coated CS-Biotin21.8%/Insulin polyelectrolyte complex presenting the best performance. In conclusion, biotin decorated muco-inert nanocomplexes with HA coating are a promising platform for oral insulin delivery.


Subject(s)
Biotin/metabolism , Drug Carriers/chemical synthesis , Drug Delivery Systems/methods , Enterocytes/metabolism , Insulin/administration & dosage , Mucus/metabolism , Administration, Oral , Animals , Biotin/chemistry , Cell Membrane Permeability/drug effects , Cells, Cultured , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/therapeutic use , Enterocytes/drug effects , Hyaluronic Acid/chemistry , Hyaluronic Acid/metabolism , Hypoglycemic Agents/administration & dosage , Insulin/pharmacokinetics , Intestinal Absorption/drug effects , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Mucus/drug effects , Nanoparticles/chemistry , Nanoparticles/metabolism , Nanoparticles/therapeutic use , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/therapeutic use , Rats , Rats, Sprague-Dawley , Swine
10.
J Biomed Mater Res A ; 109(5): 804-813, 2021 05.
Article in English | MEDLINE | ID: mdl-32720439

ABSTRACT

Due to their simple crystal structures, one-dimensional hydroxyapatite (HA) nanostructures are easily to be applied to understand the fundamental concepts about the influences of HA dimensionality on physical, chemical, and biological properties. So, in this work, three typical HA one-dimensional nanostructures, HA nanotubes, HA nanowires, and HA nanospheres, were prepared, whose theoretical structures were built also. in vitro cytocompatibility test proved that, contrasting with TCPS, HA one-dimensional nanostructures had certain degree of cytotoxicity because HA nanostructures increase the generation of intracellular reactive oxygen species (ROS) and intracellular calcium. Theoretical simulation indicated that HA nanosphere has higher intracellular ROS generation and lower ROS storage amount than HA nanowire and HA nanotube, which were the possible reasons for its stronger cytotoxicity. Among these typical one-dimensional nanostructures, owing to higher drug storage amount and sustained delivery ability, HA nanotube was more potential application in orthopedics. The tubular structure of HA nanotubes could be used as reservoirs for small molecule drugs or growth factors. The cytocompatibility of HA nanostructures can be improved obviously when they were produced into two-dimensional structures. The prepared multilayer structure can simulate lamellar structures of Harvard system and enhance the cytocompatibility of Ti substrate. Therefore, the method used in this work is a prospective method to improve the inherently bio-inert of Ti when used in hard tissue repairing.


Subject(s)
Coated Materials, Biocompatible/pharmacology , Durapatite/chemistry , Nanostructures/chemistry , Animals , Animals, Newborn , Calcium/metabolism , Coated Materials, Biocompatible/toxicity , Drug Delivery Systems , Drug Liberation , Durapatite/pharmacology , Durapatite/toxicity , Materials Testing , Nanotubes/chemistry , Nanowires/chemistry , Osteoblasts/drug effects , Osteoblasts/metabolism , Rats , Reactive Oxygen Species/metabolism , Skull/cytology , Spectroscopy, Fourier Transform Infrared , Vancomycin/administration & dosage
11.
Biomater Sci ; 8(23): 6786-6797, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33146657

ABSTRACT

Liposomes are promising vectors for pulmonary drug delivery, and have been used in marketed inhalation products. Membrane fluidity is an important property of liposomes. However, the influence of liposome membrane fluidity on its interaction with pulmonary physiological barriers is still unclear and needs elucidation. Here, a series of PEGylated DPPC (1,2-dihexadecanoyl-rac-glycero-3-phosphocholine) liposomes with different membrane fluidity were prepared, and their interaction with different pulmonary physiological barriers, including the mucus permeation capacity, macrophage uptake, trachea distribution and retention behavior, was investigated. The liposomes exhibited sizes of around 100 nm, near-neutral surface charge, and the membrane fluidity increased with increasing cholesterol ratio. In vitro studies showed that the liposomes with lower membrane fluidity presented optimal mucus permeation efficiency, while those with higher membrane fluidity displayed lower macrophage uptake. An in vivo trachea distribution study revealed that liposomes with low or medium membrane fluidity exhibited enhanced trachea permeation. No significant difference in lung retention was found among these liposomes. In conclusion, the mucus permeation and macrophage phagocytosis behavior of liposomes could be well tuned by changing their membrane fluidity.


Subject(s)
Drug Delivery Systems , Liposomes , Membrane Fluidity , Cholesterol , Lung
12.
Eur J Pharm Biopharm ; 155: 139-146, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32853695

ABSTRACT

Sustained drug delivery is considered as an effective strategy to improve the treatment of local lung diseases. In this context, inhalation administration of large porous microparticles (LPPs) represents promising prospects. However, one major challenge with said delivery technology is to control the drug release pattern (especially to decrease the burst release) while maintaining a low mass density/high porosity, which is of high significance for the aerodynamic behavior of LPP systems. Here, we show how to engineer drug-loaded, biodegradable LPPs with varying microstructure by means of a premix membrane emulsification-solvent evaporation (PME-SE) method using poly(vinyl pyrrolidone) (PVP) as the pore former. The influence of PVP concentration on the physicochemical properties, in-vitro drug release behavior and in-vitro aerodynamic performance of the drug-loaded microparticles was tested. We demonstrated that the PME-SE technique led to LPPs with favorable pore distribution characteristics (i.e., low external but high internal porosity) as a function of the PVP concentration. In general, more PVP conditioned a larger discrepancy of the internal vs. external porosity. When the external porosity of the LPP formulation (15% of PVP during the manufacturing process) was less than 3%, the burst release of the embedded drug was significantly reduced compared to LPPs prepared by a "conventional" emulsification solvent evaporation method. All the formulations prepared by the PME-SE method had aerodynamic properties suitable for inhalation. This is the first report indicating that the microstructure of LPPs can be tailored using the PME-SE technology with PVP as a suitable pore former. Doing so, we designed LPP formulations having full control over the drug release kinetics and aerodynamic behavior.


Subject(s)
Chemical Engineering/methods , Microspheres , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/chemical synthesis , Pyrazoles/chemical synthesis , Pyridines/chemical synthesis , Administration, Inhalation , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokinetics , Porosity , Pyrazoles/administration & dosage , Pyrazoles/pharmacokinetics , Pyridines/administration & dosage , Pyridines/pharmacokinetics
13.
J Control Release ; 321: 641-653, 2020 05 10.
Article in English | MEDLINE | ID: mdl-32097672

ABSTRACT

Macromolecular drugs, characterized by low stability and large molecular weight, still faced various difficulties by oral administration. And controlling drugs' release rate to reach the physiological concentration in the blood was recognized as one of the main challenges in this field but no studies are available so far. Thus, the objective of this study was to investigate the effect of insulin release rate on its in vitro and in vivo behavior when other obstacles (drug stability, mucus penetration and retention in gastrointestinal tract) was firstly overcome. Using n-butylcyanoacrylate (BCA) as the carrier, insulin-loaded Poly (n-butylcyanoacrylate) nanoparticles (Ins/PBCA NPs) were prepared by self-polymerization and the release rate of insulin was controlled by adjusting the mass ratio of Insulin/BCA. The NPs exhibited good stability in gastric fluid with controlled release in intestine and the release rate increased with the increase of Insulin/BCA mass ratio. All the Ins/PBCA NPs with different release rate showed excellent mucus penetration (>60%, 10 min) and strong gastrointestinal retention (~70%, 12 h). Especially, all the NPs showed promising hypoglycemic effect with the extent depending on drug release rate. Ins/BCA = 2/10 NPs exhibited fast hypoglycemic effect, while Ins/BCA = 2/15 NPs showed slow and outstanding performance. In conclusion, Ins/PBCA NPs could not only overcome the oral barriers of insulin delivery but also provide desired hypoglycemic effect by controlling insulin release rate.


Subject(s)
Drug Carriers , Enbucrilate , Insulin , Nanoparticles , Administration, Oral , Delayed-Action Preparations , Diabetes Mellitus/drug therapy , Insulin/administration & dosage , Polymerization
14.
Zhong Xi Yi Jie He Xue Bao ; 7(4): 342-8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19361364

ABSTRACT

OBJECTIVE: To observe the effects of berberine on osteoclastic differentiation and bone resorption action in vitro, and to investigate the cellular mechanism of its inhibitory effects on bone resorption. METHODS: The multinucleated osteoclasts (MNCs) were derived by 1,25-dihydroxyvitamin D3 and dexamethasone from bone marrow cells in the coculture system with primary osteoblastic cells. The tartrate-resistant acid phosphatase (TRAP) staining and image analysis of bone resorption pit on dental slices were used to identify osteoclast. The activity of TRAP was measured by p-nitrophenyl sodium phosphate assay. The bone resorption pit area on the bone slices formed by osteoclasts was measured by computer image processing. RESULTS: At the concentrations of 0.1, 1 and 10 micromol/L, berberine dose-dependently suppressed the formation of TRAP-positive multinucleated cells, the TRAP activity and the osteoclastic bone resorption. The strongest inhibitory effect was exhibited at the concentration of 10 micromol/L, with the inhibiting rate of 60.45%, 42.12% and 72.69% respectively. CONCLUSION: Berberine can decrease bone loss through inhibition of osteoclast formation, differentiation and bone resorption.


Subject(s)
Berberine/pharmacology , Bone Resorption/metabolism , Cell Differentiation/drug effects , Osteoclasts/drug effects , Acid Phosphatase/metabolism , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Cells, Cultured , Isoenzymes/metabolism , Osteoclasts/cytology , Rats , Rats, Sprague-Dawley , Tartrate-Resistant Acid Phosphatase
15.
Eur J Pharm Biopharm ; 143: 70-79, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31446045

ABSTRACT

Controlled drug delivery to the lungs is promising with plentiful advantages over current rapid release products. However, alveolar macrophage clearance has severely hindered the application of inhaled controlled release preparations. The objective of our study was to explore the feasibility to decorate poly(lactide-co-glycolide) (PLGA) microparticles with endogenous phospholipids found in the deep lungs, thus, to regulate the interplay with alveolar macrophages. The influence of the phospholipid amount and type on macrophage uptake of PLGA microparticles was investigated systemically under both in vitro (RAW264.7 and NR8383) and in vivo conditions. The uptake rate (k) by macrophages, in vivo elimination rate from the bronchoalveolar lavage fluid (k') and elimination rate from the whole lung (k″) were used as parameters for evaluation. Our data showed that a modification with dipalmitoyl phosphatidylcholine (DPPC) enhanced the macrophage phagocytosis significantly over the unmodified counterparts. Thereafter, using the same modification ratio, remarkable enhancement of macrophage uptake was found in the presence of different types of other phospholipids, especially with distearoyl phosphatidylethanolamine (DSPE). When replaced by a poly(ethylene glycol)-conjugated version of DSPE the uptake of the modified PLGA microparticles was reduced by ~200%. Meanwhile, the drug content in the lung tissue was improved by 3-fold (area under the curve value). Finally, it was possible to establish a correlation between in vitro phagocytosis and in vivo lung elimination rate for the investigated formulations. Overall, our study demonstrated that phospholipids play an important role in modulating the clearance of microparticle-based drug delivery vehicles, which gives a meaningful insight into the development of prolonged drug release system for inhalation.


Subject(s)
Macrophages, Alveolar/metabolism , Phospholipids/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Administration, Inhalation , Animals , Cell Line , Delayed-Action Preparations/chemistry , Drug Delivery Systems/methods , Lung/metabolism , Mice , Phagocytosis/drug effects , Phosphatidylglycerols/chemistry , Polyethylene Glycols/chemistry , RAW 264.7 Cells
16.
Res Aging ; 37(4): 388-412, 2015 May.
Article in English | MEDLINE | ID: mdl-25651576

ABSTRACT

The goal of this study was to investigate individual and contextual factors associated with dental care utilization by U.S. informal caregivers. The sample included all 2010 Behavioral Risk Factor Surveillance System respondents who completed the caregiver module and reported providing care for 1 year or more to an individual aged ≥ 50 years or older (n = 1,196). Multiple logistic regressions were used to examine associations of caregiver and care characteristics and county-level contextual characteristics (from Area Resource File data) with two outcomes: dental visits and dental cleaning during previous year. Caregivers with health insurance coverage and higher education were more likely to use dental care; those who had lost more teeth and who were spouse caregivers were less likely to do so. Community characteristics were not correlated with caregivers' use of dental care. Our findings suggest that better access to dental care could improve dental care utilization by caregivers.


Subject(s)
Caregivers/statistics & numerical data , Dental Care/statistics & numerical data , Health Knowledge, Attitudes, Practice , Behavioral Risk Factor Surveillance System , Female , Humans , Logistic Models , Male , Middle Aged , Risk Factors , United States/epidemiology
17.
PLoS One ; 7(2): e31157, 2012.
Article in English | MEDLINE | ID: mdl-22363569

ABSTRACT

Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor beta 1 (TGF-ß(1)). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-ß(1), MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.


Subject(s)
Cicatrix, Hypertrophic/drug therapy , Ear/pathology , Ligusticum/chemistry , Oils, Volatile/therapeutic use , Animals , Caspase 3/genetics , Caspase 3/metabolism , Caspase 9/genetics , Caspase 9/metabolism , Chemistry, Pharmaceutical , Cicatrix, Hypertrophic/enzymology , Cicatrix, Hypertrophic/genetics , Collagen Type I/metabolism , Collagen Type III/metabolism , Disease Models, Animal , Female , Gene Expression Regulation/drug effects , Humans , In Situ Nick-End Labeling , Liposomes , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Oils, Volatile/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits , Staining and Labeling , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
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