In vitro and in vivo evaluation of clastogenicity of second-line antitubercular drug loaded PLGA nanoparticles

2020 ◽  
pp. 096032712097934
Author(s):  
Avaneesh Kumar Pandey ◽  
Rajendra Kumar ◽  
Nusrat Shafiq ◽  
Ritika Kondel ◽  
Shanky Garg ◽  
...  
Keyword(s):  
Micronucleus Assay ◽  
Plga Nanoparticles ◽  
Second Line ◽  
Cho Cell ◽  
In Vivo Evaluation ◽  
Antitubercular Drugs ◽  
Significant Difference ◽  
In Vitro Micronucleus Assay

Sustained release nanoformulations of second line antitubercular drugs levofloxacin and ethionamide had shown promise in pharmacokinetics and acute and sub-acute toxicity studies. The present study evaluated the clastogenicity potential of the nanoformulations of these antitubercular agents. Clastogenicity was evaluated by (a) in vitro micronucleus assay (b) in vivo micronucleus assay in Swiss albino mice and (c) sister chromatid exchange (SCE) in CHO cell lines. Ethionamide and levofloxacin loaded nanoparticles were 312 ± 64 nm and 245 ± 24 nm in size respectively and drug encapsulation was 35.2 ± 3.1% w/w and 45.6 ± 9.4% w/w, respectively. The frequency of MN-NCE/1000 NCE and MN-PCE/1000 PCE were significantly reduced in mice treated with ethionamide nanoparticle (3.5 ± 0.9, 13.8 ± 16.68) and levofloxacin nanoparticles (5.6 ± 2.7, 16.7 ± 12.7) compared to the mice treated with free ethionamide (11.5 ± 4.1, p = 0.23 and 45.19 ± 19.21, p = 0.38) and free levofloxacin (14.7 ± 1.88, p < 0.0001 and 54.6 ± 18.1, p = 0.0017), respectively. For in vitro, micronucleus assay frequencies of micronuclei per thousand bi-nucleated cells (MN-BN/1000 BN) was 188.3 ± 20.20 and 148 ± 20.42 for ethionamide and levofloxacin nanoparticles as compared to 232.6 ± 16.04 (p = 0.52) and 175 ± 5.56 (p = 0.45) for free ethionamide and levofloxacin, respectively. The average number of SCE per cell for nanoformulation of ethionamide were not different from that of free drug (4.9 ± 0.51 vs 4.1 ± 0.55, p = 0.86). The SCE per cells were not significant difference for nanoformulation of levofloxacin (2.33 ± 1.36 vs 5.46 ± 0.25, p = 0.88). In vitro and in vivo assays have shown relatively less clastogenic potential of equivalent dose of ethionamide nanoparticles as compared to the conventional formulation.

scholarly journals Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Rajni Bala ◽  
Sushil Khanna ◽  
Pravin Pawar
Keyword(s):  
Tensile Strength ◽  
Drug Release ◽  
Content Uniformity ◽  
In Vivo Evaluation ◽  
Disintegration Time ◽  
Significant Difference ◽  
Film Formulation ◽  
Test Film

Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of Cmax (95.87%), tmax (71.42%), AUC0−t (98.125%), and AUC0−∞ (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles.

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits

2020 ◽  
Vol 26 (44) ◽  
pp. 5755-5763
Author(s):  
Kaleem Ullah ◽  
Shujaat Ali Khan ◽  
Muhammad Sohail ◽  
Abdul Mannan ◽  
Ghulam Murtaza
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Oral Solution ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Significant Difference

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

PLGA nanoparticles for nose to brain delivery of Clonazepam: formulation, optimization by 32 Factorial design, in vitro and in vivo evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Pranav Shah ◽  
Jayant Sarolia ◽  
Bhavin Vyas ◽  
Priti Wagh ◽  
Kaul Ankur ◽  
...  
Keyword(s):  
Particle Size ◽  
Factorial Design ◽  
Intranasal Administration ◽  
Plga Nanoparticles ◽  
Brain Targeting ◽  
Rabbit Brain ◽  
Histopathological Study ◽  
In Vivo Evaluation

Background: Intranasal administration of biodegradable nanoparticles has been extensively studied for targeting the drug directly to CNS through olfactory or trigeminal route bypassing blood brain barrier. Objective: The objective of the present study was to optimize Clonazepam loaded PLGA nanoparticles (CLO-PNPs) by investigating the effect of process variables on the responses using 32 full factorial design. Methods: Effect of two independent factors-amount of PLGA and concentration of Poloxamer 188, were studied at low, medium and high levels on three dependent responses-%Entrapment efficiency, Particle size (nm) and %cumulative drug release at 24hr. Results: %EE, Particle size and %CDR at 24hr of optimized batch was 63.7%, 165.1 nm and 86.96% respectively. Nanoparticles were radiolabeled with 99mTc and biodistribution was investigated in BALB/c mice after intranasal & intravenous administrations. Significantly higher brain/blood uptake ratios and AUC values in brain following intranasal administration of CLO-PNPs indicated more effective brain targeting of CLO. Higher brain uptake of intranasal CLO-PNPs was confirmed by rabbit brain scintigraphy imaging. Histopathological study performed on goat nasal mucosa revealed no adverse response of nanoparticles. TEM image exhibited spherical shaped particles in nano range. DSC and XRD studies suggested Clonazepam encapsulation within PLGA matrix. The onset of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as compared to intranasal & intravenous CLO-SOL. Conclusion: This investigation exhibits rapid rate and higher extent of CLO transport in brain with intranasal CLO-PNPs suggesting a better option as compared to oral & parenteral route in management of acute status epilepticus.

Genotoxic evaluation of five Angiotesin II receptor blockers: In vivo and in vitro micronucleus assay

2014 ◽  
Vol 767 ◽  
pp. 1-7 ◽  
Author(s):  
Iratxe Huerta ◽  
Maitane Barasoain ◽  
Mercedes Télez ◽  
Mikel Longa ◽  
Javier Muga ◽  
...  
Keyword(s):  
Micronucleus Assay ◽  
Receptor Blockers ◽  
In Vitro Micronucleus Assay

Experiments in the EpiDerm 3D Skin In Vitro Model and Minipigs In Vivo Indicate Comparatively Lower In Vivo Skin Sensitivity of Topically Applied Aneugenic Compounds

2021 ◽  
Author(s):  
Maik Schuler ◽  
Lindsay Tomlinson ◽  
Michael Homiski ◽  
Jennifer Cheung ◽  
Yutian Zhan ◽  
...  
Keyword(s):  
Human Skin ◽  
Kinase Inhibitors ◽  
Micronucleus Assay ◽  
Hazard Identification ◽  
Response Analysis ◽  
Nuclear Area ◽  
Ki 67 ◽  
In Vitro Micronucleus Assay

Abstract Risk management of in vitro aneugens for topically applied compounds is not clearly defined because there is no validated methodology to accurately measure compound concentration in proliferating stratum basale keratinocytes of the skin. Here, we experimentally tested several known aneugens in the EpiDerm reconstructed human skin in vitro micronucleus assay and compared the results to flow cytometric mechanistic biomarkers (phospho-H3; MPM2, DNA content). We then evaluated similar biomarkers (Ki-67, nuclear area) using immunohistochemistry in skin sections of minipigs following topical exposure the potent aneugens, colchicine, and hesperadin. Data from the EpiDerm model showed positive micronucleus responses for all aneugens tested following topical or direct media dosing with similar sensitivity when adjusted for applied dose. Quantitative benchmark dose-response analysis exhibited increases in the mitotic index biomarkers phospho-H3 and MPM2 for tubulin binders and polyploidy for aurora kinase inhibitors are at least as sensitive as the micronucleus endpoint. By comparison, the aneugens tested did not induce histopathological changes, increases in Ki-67 immunolabeling or nuclear area in skin sections from the in vivo minipig study at doses in significant excess of those eliciting a response in vitro. Results indicate the EpiDerm in vitro micronucleus assay is suitable for the hazard identification of aneugens. The lack of response in the minipig studies indicates that the barrier function of the minipig skin, which is comparable to human skin, protects from the effects of aneugens in vivo. These results provide a basis for conducting additional studies in the future to further refine this understanding.

In vitro and in vivo evaluation of Δ9-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy

2015 ◽  
Vol 487 (1-2) ◽  
pp. 205-212 ◽  
Author(s):  
L. Martín-Banderas ◽  
I. Muñoz-Rubio ◽  
J. Prados ◽  
J. Álvarez-Fuentes ◽  
J.M. Calderón-Montaño ◽  
...  
Keyword(s):  
Cancer Chemotherapy ◽  
Plga Nanoparticles ◽  
In Vivo Evaluation

scholarly journals Improved accuracy of digital implant impressions with newly designed scan bodies: an in vivo evaluation in beagle dogs

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruoxuan Huang ◽  
Yuanxiang Liu ◽  
Baoxin Huang ◽  
Fengxing Zhou ◽  
Zhuofan Chen ◽  
...  
Keyword(s):  
Beagle Dogs ◽  
In Vivo Evaluation ◽  
Group I ◽  
Digital Impressions ◽  
Significant Difference ◽  
Extensional Structure ◽  
The Mean ◽  
Group Ii

Abstract Background The accuracy of digital impressions for fully edentulous cases is currently insufficient for routinely clinical application. To overcome the challenge, a modified scan body was introduced, which demonstrated satisfactory accuracy in vitro. The aim of this study was to evaluate the accuracy of digital impressions using the modified scan bodies with extensional structure versus scan bodies without extensional structure in mandible with two implants in beagle dogs. Methods The unilateral mandibular second premolar to second molar were extracted in four beagle dogs. Twelve weeks later, two implants were placed. Five repeated digital impressions were performed with an intraoral scanner on each dog using each of the two different scan bodies: Group I—scan body without extensional structure (SB); Group II—scan body with extensional structure (SBE). The scans were exported to Standard Tessellation Language (STL) files to serve as test data. The dogs were sacrificed and the dissected mandibles were digitalized with a lab scanner to provide reference data. Linear and angular deviations were calculated in an inspection software for accuracy assessment. Statistical analysis was performed with two-way ANOVA. The level of significance was set at α = 0.05. Results For trueness assessment, the mean of absolute linear/angular deviations were 119.53 μm/0.75 degrees in Group I and 68.89 μm/0.36 degrees in Group II. SBE was more accurate than SB regarding both linear (p = 0.008) and angular (p = 0.049) deviations. For precision assessment, the mean of absolute linear/angular deviations were 63.01 μm/0.47 degrees in Group I and 38.38 μm/0.24 degrees in Group II. No significant difference was found. Conclusions The application of SBE significantly improved the trueness of digital impressions in mandible with two implants compared to SB. No significant difference was found in terms of precision.

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