scholarly journals Biocompatible Hydrogel for Intra-Articular Implantation Comprising Cationic and Anionic Polymers of Natural Origin: In Vivo Evaluation in a Rabbit Model

Polymers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 4426
Author(s):  
Karina L. Bierbrauer ◽  
Roxana V. Alasino ◽  
Fernando E. Barclay ◽  
Eduardo M. Belotti ◽  
Hugo H. Ortega ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Rabbit Model ◽  
Left Knee ◽  
In Vivo Studies ◽  
In Vivo Evaluation ◽  
Group A ◽  
Group B ◽  
The Right

We describe the functional capability of a cross-linked hydrogel composed of sulfated glycosaminoglycans and a cationic cellulose by conducting trials on experimental animal models using intra-articular implants to treat an articular disease called osteoarthritis. Forty-eight mature New Zealand white rabbits were divided into three experimental groups: A, B, and C. Group A and B underwent unilateral anterior cruciate ligament transection (ACLT) of the right knee. Subsequently, both knees of group A were treated with the injectable formulation under study. Meanwhile, group B was treated with sterile PBS (placebo). The animals of group C were surgically operated in both knees: Commercial hyaluronic acid (HA) was implanted in the left knee, and the formulation under study was implanted in the right knee. After implantation, all specimens underwent several evaluations at 3, 6, and 12 months postoperatively. At 6 months, no significant differences were detected between the right and left knees of the different groups. However, significant differences were observed between both knees at 12 months in group C, with less cartilage damage in the right knees implanted with our hydrogel. Therefore, in vivo studies have demonstrated hydrogel safety, superior permanence, and less cartilage damage for long-term follow up 12 months after implantation for the formulation under study compared with commercial HA.

scholarly journals RADIOLOGICAL STUDY OF MEGACOLON IN TRYPANOSOMA CRUZI INFECTED RATS

2018 ◽  
Vol 31 (1) ◽  
Author(s):  
Carlos Edmundo Rodrigues FONTES ◽  
Ana Paula de ABREU ◽  
Aretuza Zaupa GASPARIM
Keyword(s):  
Trypanosoma Cruzi ◽  
Wistar Rats ◽  
In Vivo Studies ◽  
Proposed Model ◽  
Male Wistar Rats ◽  
Group A ◽  
Time Of Infection ◽  
Group B ◽  
Digital Caliper

ABSTRACT Background: Researches on Chagas disease still use several animals and rats, due to size and susceptibility were preferred by many authors. Aim: To develop an experimental model of megacolon in rats inoculated with the strain Y of Trypanosoma cruzi. Methods: Thirty male Wistar rats were distributed in three groups inoculated with different inoculants: Group A: 600000, Group B: 1000000 and Group C: 1500000 blood trypomastigotes of T. cruzi. Animals were sedated intramuscularly at zero inoculation time (T0) and 60 days after inoculation (T60), to perform the barium enema in order to evaluate the dilatation of the different segments of colon in a comparative study of the measurements obtained, using a digital caliper. Evidence of infection was performed by blood smear collected from the animal’s tail 18 days after inoculation with observation of blood forms. Results: Comparing the intestinal diameter of the inoculated animals with 60,0000 trypomastigotes in the T0 of infection with T60 days after the inoculation, significant dilatation was observed between the proximal, medial and distal segments (p<0.01), indicating the establishment of the megacolon model. In addition, comparing intestinal diameter between the different segments, with in the T0 of infection and the T60 after inoculation, significant alterations were observed (p<0.05). Conclusion: The proposed model was possible for in vivo studies of alterations due to infection by T. cruzi and functional alterations of the colon. In addition, the changes manifested in the colon are not directly proportional to the size of the inoculum, but to the time of infection that the animals were submitted, since the animals inoculated with 60,0000 blood forms were the ones which presented the most significant alterations.

scholarly journals Baicalein Inhibits MMPs Expression via a MAPK-Dependent Mechanism in Chondrocytes

2015 ◽  
Vol 36 (1) ◽  
pp. 325-333 ◽  
Author(s):  
Wei-Ping Chen ◽  
Yan Xiong ◽  
Peng-Fei Hu ◽  
Jia-Peng Bao ◽  
Li-Dong Wu
Keyword(s):  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Cartilage Damage ◽  
Rabbit Model ◽  
Mitogen Activated Protein Kinase ◽  
Scutellaria Baicalensis Georgi ◽  
The Matrix ◽  
Mitogen Activated Protein

Background: Baicalein is a flavonoid isolated from Scutellaria baicalensis Georgi. Here, we investigated the anti-osteoarthritic effect of baicalein in vitro and in vivo. Methods: Interleukin-1 beta (IL-1β)-induced chondrocytes were treated with different concentrations of baicalein, real-time PCR and ELISA were performed to detect the matrix metalloproteinases (MMPs) expression. Western blot was used to evaluate the mitogen-activated protein kinase (MAPK) expression. In experimental osteoarthritis (OA), rabbits were treated with baicalein, gross morphological and histological assessment was performed to evaluate the cartilage damage. Results: Baicalein significantly reduced the expression of MMPs in vitro and in vivo. Moreover, baicalein significantly reduced the phosphorylation of p38 and extracellular signal regulated kinase (ERK), but not of c-Jun N-terminal kinase (JNK). In addition, intra-articular injection of baicalein ameliorated the cartilage damage in a rabbit model of OA induced by anterior cruciate ligament transection (ACLT). Conclusions: The results indicate that baicalein may be considered as a potential agent for OA treatment.

In vivo intervertebral disc regeneration using stem cell–derived chondroprogenitors

2009 ◽  
Vol 10 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Hormoz Sheikh ◽  
Karen Zakharian ◽  
Ramiro Perez De La Torre ◽  
Christopher Facek ◽  
Adrian Vasquez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mr Imaging ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Rabbit Model ◽  
Imaging Studies ◽  
Notochordal Cell ◽  
Group A ◽  
Group B

Object There is currently no biologic therapy to repair or restore a degenerated intervertebral disc. A potential solution may rest with embryonic stem cells (ESCs), which have a potential to grow indefinitely and differentiate into a variety of cell types in vitro. Prior studies have shown that ESCs can be encouraged to differentiate toward specific cell lineages by culture in selective media and specific growth environment. Among these lineages, there are cells capable of potentially producing nucleus pulposus (NP) in vivo. In this investigation, the authors studied ESCderived chondroprogenitors implanted into a degenerated disc in a rabbit. For this purpose, a rabbit model of disc degeneration was developed. Methods A percutaneous animal model of disc degeneration was developed by needle puncture of healthy intact discs in 16 New Zealand white rabbits. Series of spine MR imaging studies were obtained before disc puncture and after 2, 6, and 8 weeks. Prior to implantation, murine ESCs were cultured with cis-retinoic acid, transforming growth factor β, ascorbic acid, and insulin-like growth factor to induce differentiation toward a chondrocyte lineage. After confirmation by MR imaging, degenerated disc levels were injected with chondrogenic derivatives of ESCs expressing green fluorescent protein. At 8 weeks post-ESC implantation, the animals were killed and the intervertebral discs were harvested and analyzed using H & E staining, confocal fluorescent microscopy, and immunohistochemical analysis. Three intervertebral disc groups were analyzed in 16 rabbits, as follows: 1) Group A, control: naïve, nonpunctured discs (32 discs, levels L4–5 and L5–6); 2) Group B, experimental control: punctured disc (16 discs, level L2–3); and 3) Group C, experimental: punctured disc followed by implantation of chondroprogenitor cells (16 discs, level L3–4). Results The MR imaging studies confirmed intervertebral disc degeneration at needle-punctured segments starting at ~ 2 weeks. Postmortem H & E histological analysis of Group A discs showed mature chondrocytes and no notochordal cells. Group B discs displayed an intact anulus fibrosus and generalized disorganization within fibrous tissue of NP. Group C discs showed islands of notochordal cell growth. Immunofluorescent staining for notochordal cells was negative for Groups A and B but revealed viable notochordal-type cells within experimental Group C discs, which had been implanted with ESC derivatives. Notably, no inflammatory response was noted in Group C discs. Conclusions This study illustrates a reproducible percutaneous model for studying disc degeneration. New notochordal cell populations were seen in degenerated discs injected with ESCs. The lack of immune response to a xenograft of mouse cells in an immunocompetent rabbit model may suggest an as yet unrecognized immunoprivileged site within the intervertebral disc space.

DeVega versus ring annuloplasty in severe functional tricuspid insufficiency and their impact on the right ventricle

2019 ◽  
Vol 1 (4) ◽  
pp. 133-139
Author(s):  
Yasser Hamdy ◽  
Mohammed Mahmoud Mostafa ◽  
Ahmed Elminshawy
Keyword(s):  
Right Ventricular ◽  
Tricuspid Valve ◽  
Tricuspid Regurgitation ◽  
Early Postoperative Period ◽  
Tricuspid Valve Repair ◽  
Ring Annuloplasty ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
The Right

Background: Functional tricuspid valve regurgitation secondary to left-sided valve disease is common. DeVega repair is simple, but residual regurgitation with subsequent impairment of the right ventricular function is a concern. This study aims to compare tricuspid valve repair using DeVega vs. ring annuloplasty and their impact on the right ventricle in the early postoperative period and after six months. Methods: This is a prospective cohort study of 51 patients with rheumatic heart disease who underwent tricuspid valve repair for secondary severe tricuspid regurgitation. Patients were divided into two groups: group A; DeVega repair (n=34) and group B; ring annuloplasty repair (n=17). Patients were assessed clinically and by echocardiography before discharge and after six months for the degree of tricuspid regurgitation, right ventricular diameter and tricuspid annular plane systolic excursion (TAPSE). Results: Preoperative echocardiographic assessment showed no difference in left ventricular end-systolic diameter, end-diastolic diameter, ejection fraction and right ventricular diameter, however; group A had significantly better preoperative right ventricular function measured by TAPSE (1.96 ± 0.27 vs1.75 ± 0.31 cm; p=0.02). Group B had significantly longer cardiopulmonary bypass time (127.65 ± 13.56 vs. 111.74 ± 18.74 minutes; p= 0.003) and ischemic time (99.06 ± 11.80 vs. 87.15 ± 16.01 minutes; p= 0.009). Pre-discharge, there was no statistically significant difference in the degree of tricuspid regurgitation, but the right ventricular diameter was significantly lower in group B (2.66 ± 0.41 and 2.40 ± 0.48 cm; p=0.049). After six months of follow up, the degree of tricuspid regurgitation (p= 0.029) and the right ventricular diameter were significantly lower in the ring annuloplasty group (2.56 ± 0.39 and 2.29 ± 0.44 cm; p=0.029). Although there was a statistically significant difference in preoperative TAPSE, this difference disappeared after six months. Conclusion: Both DeVega and ring annuloplasty techniques were effective in the early postoperative period, ring annuloplasty was associated with lesser residual regurgitation and better right ventricular remodeling in severe functional tricuspid regurgitation than DeVega procedure after 6-months of follow up.

Formulation and In Vivo Evaluation of Mucoadhesive Micro-spheres of Rebamipide, a Mucoprotective Drug for GIT Disorders

2018 ◽  
Vol 11 (3) ◽  
pp. 4089-4097
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Amino Acid Derivative ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
In Vitro Drug Release ◽  
Percentage Yield

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  

Cationic Diclofenac Lipid Nanoemulsion for Improved Oral Bioavailability: Preparation, Characterization and In Vivo Evaluation

2015 ◽  
Vol 8 (2) ◽  
pp. 2874-2880
Author(s):  
Kishan Veerabrahma ◽  
Swapna Madishetty ◽  
Muzammil Afzal Syed ◽  
Prabhakar Kandadi
Keyword(s):  
Oral Bioavailability ◽  
Physical Stability ◽  
Cationic Lipid ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Drug Content ◽  
Lipid Nanoemulsion

Cationic nanoemulsions were reported to have increased bioavailability. The aim of present study was to prepare a cationic lipid nanoemulsion of diclofenac acid (LNEs) for improved oral bioavailability to treat arthritic conditions. The LNEs of diclofenac acid were prepared by using soya bean oil, egg lecithin, cholesterol and stearylamine. Stearylamine was used as positive charge inducer. The LNEs were processed by homogenization and ultrasonication. The formulation composition was selected based on earlier reports. The LNEs were characterized for size and zeta potential. The physical stability of LNEs was studied using autoclaving, centrifugal, desorption (dilution effect) stresses and on storage. The total drug content and entrapment efficiency were determined using HPLC. During in vivo studies in Wistar rats, the pharmacokinetic parameters of LNEs were compared with a prepared diclofenac suspension in sodium CMC mucilage. The selected formulations, F1, F2 and F3, were relatively stable during centrifugal stress, dilution stress and on storage. The drug content was found to be 2.38 ± 1.70 mg/ml for F1, 2.30 ± 0.82 mg/ml for F2, and 2.45 ± 0.66 mg/ml for F3. The entrapment efficiencies were 97.83 ± 0.53%, 97.87 ± 1.22% and 98.25 ± 0.21% for F1, F2 and F3 respectively. The cumulative percentage drug release from F1, F2 and F3 showed more release in pH 6.8 phosphate buffer than in pH 1.2 HCl. During oral bioavailability studies, the LNEs showed higher serum concentrations than a suspension. The relative bioavailability of the LNE formulations F1, F2 and F3 were found to be 2.35, 2.94 and 6.28 times that of F4 suspension and were statistically significant. Of all, the cationic lipid nanoemulsion (F3) was superior in improving bioavailability, when compared with plain emulsion (F1) and cholesterol containing LNE (F2). The study helps in designing the cationic oral nanoemulsions to improve the oral bioavailability of diclofenac.

scholarly journals Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Bovine Bone ◽  
Bone Filler ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

scholarly journals Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 444
Author(s):  
Alaa Mahran ◽  
Sayed Ismail ◽  
Ayat A. Allam
Keyword(s):  
Triamcinolone Acetonide ◽  
Delivery System ◽  
Histopathological Examination ◽  
Rabbit Model ◽  
Subconjunctival Injection ◽  
In Vivo Evaluation ◽  
Ternary Phase Diagrams ◽  
Ophthalmic Delivery

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

scholarly journals Re-operation rate after surgical treatment of osteochondral lesions of the talus in paediatric and adolescent patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Daniel Körner ◽  
Christoph E. Gonser ◽  
Stefan Döbele ◽  
Christian Konrads ◽  
Fabian Springer ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Bone Grafting ◽  
Cartilage Damage ◽  
Osteochondral Lesions ◽  
Retrograde Drilling ◽  
Autologous Bone Grafting ◽  
Operation Rate ◽  
Group A ◽  
Autologous Bone ◽  
Group B

Abstract Background The aim of this study is to analyse the re-operation rate after surgical treatment of osteochondral lesions of the talus (OCLTs) in children and adolescents. Methods Between 2009 and 2019, 27 consecutive patients with a solitary OCLT (10 male, 17 female; mean age 16.9 ± 2.2 years; 8 idiopathic vs. 19 traumatic) received primary operative treatment (arthroscopy + bone marrow stimulation [BMS], n = 8; arthroscopy + retrograde drilling, n = 8; autologous chondrocyte implantation [ACI]/autologous bone grafting, n = 9; arthroscopy + BMS + retrograde drilling; n = 1; flake fixation, n = 1). Seventeen OCLTs were located at the medial and ten at the lateral talus. ‘Re-operation’ as the outcome measure was evaluated after a median follow-up of 42 months (range 6–117 months). Patients were further subdivided into groups A (re-operation, n = 7) and B (no re-operation, n = 20). Groups A and B were compared with respect to epidemiological, lesion- and therapy-related variables. Results Seven of 27 patients needed a re-operation (re-operation rate 25.9% after a median interval of 31 months [range 13–61 months]). The following operative techniques were initially used in these seven patients: arthroscopy + BMS n = 2, arthroscopy + retrograde drilling n = 4, ACI + autologous bone grafting n = 1. A comparison of group A with group B revealed different OCLT characteristics between both groups. The intraoperative findings according to the International Cartilage Repair Society (ICRS) classification revealed significantly more advanced cartilage damage in group B than in group A (p = 0.001). Conclusions We detected a re-operation rate of 25.9% after primary surgical OCLT treatment. Patients with re-operation had significantly lower ICRS classification stages compared to patients without re-operation.

scholarly journals The effect of nano-hydroxyapatite/chitosan scaffolds on rat calvarial defects for bone regeneration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Emmanouil Chatzipetros ◽  
Spyros Damaskos ◽  
Konstantinos I. Tosios ◽  
Panos Christopoulos ◽  
Catherine Donta ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Mean Value ◽  
Parietal Bone ◽  
Female Rats ◽  
Sprague Dawley ◽  
Post Surgery ◽  
Group A ◽  
The Mean ◽  
Group B ◽  
The Right

Abstract Background This study aims at determining the biological effect of 75/25 w/w nano-hydroxyapatite/chitosan (nHAp/CS) scaffolds on bone regeneration, in terms of fraction of bone regeneration (FBR), total number of osteocytes (Ost), and osteocyte cell density (CD), as well as its biodegradability. Methods Two critical-size defects (CSDs) were bilaterally trephined in the parietal bone of 36 adult Sprague-Dawley rats (18 males and 18 females); the left remained empty (group A), while the right CSD was filled with nHAp/CS scaffold (group B). Two female rats died postoperatively. Twelve, 11, and 11 rats were euthanized at 2, 4, and 8 weeks post-surgery, respectively. Subsequently, 34 specimens were resected containing both CSDs. Histological and histomorphometric analyses were performed to determine the FBR, calculated as [the sum of areas of newly formed bone in lateral and central regions of interest (ROIs)]/area of the original defect, as well as the Ost and the CD (Ost/mm2) in each ROI of both groups (A and B). Moreover, biodegradability of the nHAp/CS scaffolds was estimated via the surface area of the biomaterial (BmA) in the 2nd, 4th, and 8th week post-surgery. Results The FBR of group B increased significantly from 2nd to 8th week compared to group A (P = 0.009). Both the mean CD and the mean Ost values of group B increased compared to group A (P = 0.004 and P < 0.05 respectively). Moreover, the mean value of BmA decreased from 2nd to 8th week (P = 0.001). Conclusions Based on histological and histomorphometric results, we support that 75/25 w/w nHAp/CS scaffolds provide an effective space for new bone formation.

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