Porous Chitosan/Nano-Hydroxyapatite Composite Scaffolds Incorporating Simvastatin-Loaded PLGA Microspheres for Bone Repair

2018 ◽  
Vol 205 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Yu Li ◽  
Zhanzhao Zhang ◽  
Zhiyong Zhang
Keyword(s):  
Bone Repair ◽  
Release Kinetics ◽  
Weight Ratio ◽  
Plga Microspheres ◽  
Water Emulsion ◽  
Remarkable Effect ◽  
Porous Chitosan ◽  
Rat Calvarial Defect

The combination of bone tissue scaffolds with osteogenic induction factors is an effective strategy to facilitate bone healing processes. Here, chitosan (CS)/nano-hydroxyapatite (HA) scaffolds containing simvastatin (SIM)-loaded PLGA microspheres were fabricated by combining a freeze-drying technique with a modified water-oil-water emulsion method. The CS/HA weight ratio of 1:2 was selected by analyzing the effect of HA content on the micro-architecture, mechanical strength, and biocompatibility of the scaffold. Drug release kinetics showed that the SIM encapsulated in the scaffold was released in a sustained manner for up to 30 days. In vitro bioactivity study in rat bone marrow-derived mesenchymal stem cells showed that the SIM-loaded scaffolds had a strong ability in accelerating cell proliferation and inducing osteogenic differentiation. Moreover, an in vivo experiment using a rat calvarial defect model also documented that the SIM-loaded scaffolds had a remarkable effect on bone-promoting regeneration. The results of this study suggest that the SIM-loaded CS/HA scaffold is feasible and effective in bone repair and thus may provide a promising route for the treatment of critical-sized bone defects.

Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification In vitro and In vivo in Imaging Setups

2020 ◽  
Vol 26 (31) ◽  
pp. 3828-3833 ◽  
Author(s):  
Tuula Peñate-Medina ◽  
Eike Kraas ◽  
Kunliang Luo ◽  
Jana Humbert ◽  
Hanwen Zhu ◽  
...  
Keyword(s):  
Release Kinetics ◽  
Pure Water ◽  
Squamous Carcinoma ◽  
Peak Shift ◽  
Intensity Increase ◽  
Nude Mouse Model ◽  
Absorption And Emission ◽  
Squamous Carcinoma Cells

Background: Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. Methods: Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. Results: We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. Conclusion: Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.

scholarly journals Zn-Containing Membranes for Guided Bone Regeneration in Dentistry

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1797
Author(s):  
Manuel Toledano ◽  
Marta Vallecillo-Rivas ◽  
María T. Osorio ◽  
Esther Muñoz-Soto ◽  
Manuel Toledano-Osorio ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Bone Repair ◽  
Complex Modulus ◽  
Bacterial Colonization ◽  
Guided Bone Regeneration ◽  
M2 Macrophage

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.

scholarly journals Berberine-Coated Biomimetic Composite Microspheres for Simultaneously Hemostatic and Antibacterial Performance

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 360
Author(s):  
Xiaojian Zhang ◽  
Kaili Dai ◽  
Chenyu Liu ◽  
Haofeng Hu ◽  
Fulin Luo ◽  
...  
Keyword(s):  
In Vitro Test ◽  
Water Emulsion ◽  
Biomedical Material ◽  
Composite Microspheres ◽  
Antibacterial Performance ◽  
New Strategy ◽  
Oil In Water Emulsion ◽  
Hemostatic Powder

Biomimetic microspheres containing alginate/carboxymethylcellulose/gelatin and coated with 0%, 1%, 3%, and 6% berberine (BACG, BACG-1B, BACG-3B, BACG-6B) were prepared by the oil-in-water emulsion method combined with spray drying. Through a series of physicochemical parameters and determination of hemostatic properties in vitro and in vivo, the results indicated that BACG and BACG-Bs were effective in inducing platelet adhesion/aggregation and promoting the hemostatic potential due to their biomimetic structure and rough surface. In addition, BACG-6B with high berberine proportion presented better hemostatic performance compared with the commercial hemostatic agent compound microporous polysaccharide hemostatic powder (CMPHP). BACG-6B also showed strong antibacterial activity in the in vitro test. The hemolysis test and cytotoxicity evaluation further revealed that the novel composite biomaterials have good hemocompatibility and biocompatibility. Thus, BACG-6B provides a new strategy for developing a due-functional (hemostat/antibacterial) biomedical material, which may have broad and promising applications in the future.

Porous chitosan microspheres for application as quick in vitro and in vivo hemostat

2017 ◽  
Vol 77 ◽  
pp. 411-419 ◽  
Author(s):  
Jixiang Li ◽  
Xiaowei Wu ◽  
Yanqing Wu ◽  
Zonghao Tang ◽  
Xun Sun ◽  
...  
Keyword(s):  
Chitosan Microspheres ◽  
Porous Chitosan

scholarly journals Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride

2011 ◽  
Vol 61 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Komuravelly Someshwar ◽  
Kalyani Chithaluru ◽  
Tadikonda Ramarao ◽  
K. Kumar
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Release Kinetics ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Physical Parameters ◽  
Floating Tablets ◽  
Gastric Residence Time

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.

Preparation, Characterization and In Vitro Release Kinetics of Vancomycin Carried β-TCP/Chitosan Composite Microspheres Used as Bone Tissue Engineering Scaffolds

2012 ◽  
Vol 512-515 ◽  
pp. 1821-1825
Author(s):  
Lin Zhang ◽  
Xue Min Cui ◽  
Qing Feng Zan ◽  
Li Min Dong ◽  
Chen Wang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Cross Linking ◽  
Tissue Engineering Scaffolds ◽  
Composite Microspheres ◽  
Chitosan Composite ◽  
Vitro Release

A novel microsphere scaffolds composed of chitosan and β-TCP containing vancomycin was designed and prepared. The β-TCP/chitosan composite microspheres were prepared by solid-in-water-in-oil (s/w/o) emulsion cross-linking method with or without pre-cross-linking process. The mode of vancomycin maintaining in the β-TCP/chitosan composite microspheres was detected by Fourier transform infrared spectroscopy (FTIR). The in vitro release curve of vancomycin in simulated body fluid (SBF) was estimated. The results revealed that the pre-cross-linking prepared microspheres possessed higher loading efficiency (LE) and encapsulation efficiency (EE) especially decreasing the previous burst mass of vancomycin in incipient release. These composite microspheres got excellent sphere and well surface roughness in morphology. Vancomycin was encapsulated in composite microspheres through absorption and cross-linking. While in-vitro release curves illustrated that vancomycin release depond on diffusing firstly and then on the degradation ratio later. The microspheres loading with vancomycin would be to restore bone defect, meanwhile to inhibit bacterium proliferation. These bioactive, degradable composite microspheres have potential applications in 3D tissue engineering of bone and other tissues in vitro and in vivo.

Azole-resistant and -susceptible Aspergillus fumigatus isolates show comparable fitness and azole treatment outcome in immunocompetent mice

2017 ◽  
Vol 56 (6) ◽  
pp. 703-710
Author(s):  
Michaela Lackner ◽  
Günter Rambach ◽  
Emina Jukic ◽  
Bettina Sartori ◽  
Josef Fritz ◽  
...  
Keyword(s):  
Body Weight ◽  
Aspergillus Fumigatus ◽  
Severe Disease ◽  
Weight Ratio ◽  
Clinical Parameters ◽  
Fitness Advantage ◽  
Significant Difference ◽  
Immunocompetent Mice

Abstract No data are available on the in vivo impact of infections with in vitro azole-resistant Aspergillus fumigatus in immunocompetent hosts. Here, the aim was to investigate fungal fitness and treatment response in immunocompetent mice infected with A. fumigatus (parental strain [ps]) and isogenic mutants carrying either the mutation M220K or G54W (cyp51A). The efficacy of itraconazole (ITC) and posaconazole (PSC) was investigated in mice, intravenously challenged either with a single or a combination of ps and mutants (6 × 105 conidia/mouse). Organ fungal burden and clinical parameters were measured. In coinfection models, no fitness advantage was observed for the ps strain when compared to the mutants (M220K and G54W) independent of the presence or absence of azole-treatment. For G54W, M220K, and the ps, no statistically significant difference in ITC and PSC treatment was observed in respect to fungal kidney burden. However, clinical parameters suggest that in particular the azole-resistant strain carrying the mutation G54W caused a more severe disease than the ps strain. Mice infected with G54W showed a significant decline in body weight and lymphocyte counts, while spleen/body weight ratio and granulocyte counts were increased. In immunocompetent mice, in vitro azole-resistance did not translate into therapeutic failure by either ITC or PSC; the immune system appears to play the key role in clearing the infection.

scholarly journals Cartilage Extracellular Matrix Scaffold With Kartogenin-Encapsulated PLGA Microspheres for Cartilage Regeneration

2020 ◽  
Vol 8 ◽  
Author(s):  
Yanhong Zhao ◽  
Xige Zhao ◽  
Rui Zhang ◽  
Ying Huang ◽  
Yunjie Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Composite Scaffold ◽  
Rabbit Model ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Specific Marker ◽  
Molecular Compound ◽  
Plga Microspheres

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

scholarly journals DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Release Profile ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Release Mechanism ◽  
In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

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