scholarly journals Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Soluplus® Polymeric Micelles Encapsulating Fenbendazole

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1000 ◽  
Author(s):  
Ik Sup Jin ◽  
Min Jeong Jo ◽  
Chun-Woong Park ◽  
Youn Bok Chung ◽  
Jin-Seok Kim ◽  
...  
Keyword(s):  
Polymeric Micelles ◽  
Drug Loading ◽  
Average Particle Size ◽  
A549 Cells ◽  
Pharmacokinetic Studies ◽  
Average Particle ◽  
Severe Toxicity ◽  
Blood Concentrations

Fenbendazole (FEN), a broad-spectrum benzimidazole anthelmintic, suppresses cancer cell growth through various mechanisms but has low solubility and achieves low blood concentrations, which leads to low bioavailability. Solubilizing agents are required to prepare poorly soluble drugs for injections; however, these are toxic. To overcome this problem, we designed and fabricated low-toxicity Soluplus® polymeric micelles encapsulating FEN and conducted toxicity assays in vitro and in vivo. FEN-loaded Soluplus® micelles had an average particle size of 68.3 ± 0.6 nm, a zeta potential of −2.3 ± 0.2 mV, a drug loading of 0.8 ± 0.03%, and an encapsulation efficiency of 85.3 ± 2.9%. MTT and clonogenic assays were performed on A549 cells treated with free FEN and FEN-loaded Soluplus® micelles. The in vitro drug release profile showed that the micelles released FEN more gradually than the solution. Pharmacokinetic studies revealed lower total clearance and volume of distribution and higher area under the curve and plasma concentration at time zero of FEN-loaded Soluplus® micelles than of the FEN solution. The in vivo toxicity assay revealed that FEN-loaded Soluplus® micelle induced no severe toxicity. Therefore, we propose that preclinical and clinical safety and efficacy trials on FEN-loaded Soluplus® micelles would be worthwhile.

Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles

2017 ◽  
Vol 6 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Permender Rathee ◽  
Anjoo Kamboj ◽  
Shabir Sidhu
Keyword(s):  
Oral Bioavailability ◽  
Drug Loading ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Interaction ◽  
Precipitation Method ◽  
Pharmacokinetic Studies ◽  
Average Particle

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.

scholarly journals Sorafenib Nanomicelles Effectively Shrink Tumors by Vaginal Administration for Preoperative Chemotherapy of Cervical Cancer

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3271
Author(s):  
Jun Wang ◽  
Fengmei Lv ◽  
Tao Sun ◽  
Shoujin Zhao ◽  
Haini Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Preoperative Chemotherapy ◽  
Drug Loading ◽  
Ultrasonic Method ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Average Particle ◽  
Quality Life

To investigate the potential of sorafenib (SF) in preoperative chemotherapy for cervical cancer to reduce tumor volume, sorafenib micelles (SF micelles) with good stability and high drug loading were designed. SF micelles were prepared by film hydration followed by the ultrasonic method. The results showed that the SF micelles were spherical with an average particle size of 67.18 ± 0.66 nm (PDI 0.17 ± 0.01), a considerable drug loading of 15.9 ± 0.46% (w/w%) and satisfactory stability in buffers containing plasma or not for at least 2 days. In vitro release showed that SF was gradually released from SF micelles and almost completely released on the third day. The results of in vitro cellular intake, cytotoxicity and proliferation of cervical cancer cell TC-1 showed that SF micelles were superior to sorafenib (Free SF). For intravaginal administration, SF micelles were dispersed in HPMC (SF micelles/HPMC), showed good viscosity sustained-release profiles in vitro and exhibited extended residence in intravaginal in vivo. Compared with SF micelles dispersed in N.S. (SF micelles/N.S.), SF micelles/HPMC significantly reduced tumor size with a tumor weight inhibition rate of 73%. The results suggested that SF micelles had good potential for preoperative tumor shrinkage and improving the quality life of patients.

scholarly journals Sodium Alginate Nanoparticles of Isoniazid: Preparation and Evaluation

2019 ◽  
Vol 11 (06) ◽  
Author(s):  
Sumit Kumar ◽  
Dinesh Chandra Bhatt
Keyword(s):  
Particle Size ◽  
Sodium Alginate ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Average Particle Size ◽  
Average Particle ◽  
In Vitro Drug Release ◽  
Ionotropic Gelation ◽  
Preparation And Evaluation

Fabrication and evaluation of the Isoniazid loaded sodium alginate nanoparticles (NPs) was main objective of current investigation. These NPs were engineered using ionotropic gelation technique. The NPs fabricated, were evaluated for average particle size, encapsulation efficiency, drug loading, and FTIR spectroscopy along with in vitro drug release. The particle size, drug loading and encapsulation efficiency of fabricated nanoparticles were ranging from 230.7 to 532.1 nm, 5.88% to 11.37% and 30.29% to 59.70% respectively. Amongst all batches studied formulation F-8 showed the best sustained release of drug at the end of 24 hours.

scholarly journals Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1059
Author(s):  
Saif Ahmad Khan ◽  
Saleha Rehman ◽  
Bushra Nabi ◽  
Ashif Iqubal ◽  
Nida Nehal ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Pharmacokinetic Studies ◽  
Nanostructured Lipid Carrier ◽  
Brain Delivery ◽  
The Brain

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

scholarly journals Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 21 ◽  
Author(s):  
Yumei Lian ◽  
Xuerui Wang ◽  
Pengcheng Guo ◽  
Yichen Li ◽  
Faisal Raza ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Sodium Alginate ◽  
Primary Liver Cancer ◽  
Tumor Therapy ◽  
Average Particle Size ◽  
In Vivo Studies ◽  
Average Particle ◽  
Promising Alternative

Arsenic trioxide (ATO) has a significant effect on the treatment of acute promyelocytic leukemia (APL) and advanced primary liver cancer, but it still faces severe side effects. Considering these problems, red blood cell membrane-camouflaged ATO-loaded sodium alginate nanoparticles (RBCM-SA-ATO-NPs, RSANs) were developed to relieve the toxicity of ATO while maintaining its efficacy. ATO-loaded sodium alginate nanoparticles (SA-ATO-NPs, SANs) were prepared by the ion crosslinking method, and then RBCM was extruded onto the surface to obtain RSANs. The average particle size of RSANs was found to be 163.2 nm with a complete shell-core bilayer structure, and the average encapsulation efficiency was 14.31%. Compared with SANs, RAW 264.7 macrophages reduced the phagocytosis of RSANs by 51%, and the in vitro cumulative release rate of RSANs was 95% at 84 h, which revealed a prominent sustained release. Furthermore, it demonstrated that RSANs had lower cytotoxicity as compared to normal 293 cells and exhibited anti-tumor effects on both NB4 cells and 7721 cells. In vivo studies further showed that ATO could cause mild lesions of main organs while RSANs could reduce the toxicity and improve the anti-tumor effects. In brief, the developed RSANs system provides a promising alternative for ATO treatment safely and effectively.

Anti-Tumor Study of H6, a 4-Substituted Coumarins Derivative, Loaded Biodegradable Self-Assembly Nano-Micelles In Vitro and In Vivo

2019 ◽  
Vol 15 (7) ◽  
pp. 1515-1531 ◽  
Author(s):  
Zejiang Zhu ◽  
Zhengying Su ◽  
Jianhong Yang ◽  
Huili Liu ◽  
Minghai Tang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Therapeutic Window ◽  
Tumor Growth Inhibition ◽  
Mechanism Study ◽  
Tumor Models ◽  
Substituted Coumarins

In our previous study, we identified a class of 4-substituted coumarins as a powerful microtubule inhibitors binding to the colchicine site of β-tubulin. H6 showed potent anti-proliferative ability with IC50 values from 7 to 47 nM, and remarkable ability to reduce tumor growth in several xenograft models including taxol resistant tumor models. However, the extremely hydrophobicity limited its clinical application. In this study, to improve the anticancer activity and reduce the toxicity of H6, we successfully prepared MPEG-PCL with different proportions and H6-loaded polymeric micelles (H6/MPEG2kPCL2k micelles) by a simple thin-film hydration method. The prepared H6/MPEG-PCL micelles had a drug loading of 3.79 ± 0.001%, an encapsulation efficiency of 98.00 ± 0.41%, a mean particle size of 30.45 ± 0.18nm and a polydispersity index (PDI) of 0.096 ± 0.009. Computer simulation results revealed a good compatibility of H6 and MPEG2k-PCL2k copolymer. In in vitro release study and pharmacokinetic study showed H6 micelles can release H6 over an extended period. Furthermore, H6 micelles possessed comparative effect as free H6 in inhibiting cell growth, preventing cell migration, and inducing apoptosis. Mechanism study identified that H6 is a novel reversible microtubule inhibitor. In in vivo studies, H6 micelles exhibited tumor growth inhibition on two pulmonary metastatic tumor models (B16/F10 and 4T1). Importantly, H6 micelles significantly improved the solubility, reduced the toxicity, extended the half-life of drugs, and augmented the therapeutic window. All these results imply that H6 micelles have great potential for suppression of tumor metastasis.

scholarly journals Control of Anthracnose Disease (Colletotrichum gloeosporioides) Using Nano Chitosan Hydrolyzed by Chitinase Derived from Burkholderia cepacia Isolate E76

2018 ◽  
Vol 13 (2) ◽  
pp. 111 ◽  
Author(s):  
Yadi Suryadi ◽  
Tri Puji Priyatno ◽  
I Made Samudra ◽  
Dwi Ningsih Susilowati ◽  
Tuti Septi Sriharyani ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Colletotrichum Gloeosporioides ◽  
Sodium Tripolyphosphate ◽  
Average Particle Size ◽  
Chitosan Nanoparticles ◽  
Average Particle ◽  
Coating Application ◽  
Anthracnose Disease

<p>Anthracnose (Colletotrichum gloeosporioides) is one of the important diseases of fruit crops that need to be controlled. This study was aimed to obtain the best formula of hydrolyzed nano chitosan and its potensial in controlling anthracnose. The hydrolyzed chitosan was prepared using chitinase enzyme extracted from Burkholderia cepacia isolate E76. Chitosan nanoparticles were synthesized using ionic gelation method by reacting hydrolyzed chitosan (0.2%) with Sodium tripolyphosphate (STPP) (0.1%) as cross-linking agent using 30&amp;ndash;60 minutes stirring condition. The bioactivity of the nano chitosan formula was tested to C. gloeosporioides under in vitro and in vivo assays. The specific enzymatic activity of the purified chitinase was higher (0.19 U/mg) than that of crude enzyme (supernatant) with the purity increased by 3.8 times. Of the four formula tested, Formula A (hydrolyzed chitosan to STPP volume ratio of 5 : 1 with 60 minutes stirring condition) was found good in terms of physical characteristic of the particle. The formula nano chitosan particle had the spherical-like shape with an average particle size of 126.2+3.8 nm, polydispersity index (PI) of 0.4+0.02, and zeta potential (ZP) value of 27.8+0.2 mV. Nano chitosan had an inhibitory activity to C. gloeosporioides in vitro up to 85.7%. Moreover, it could inhibit 61.2% of C. gloeosporioides spores germination. It was shown that nano chitosan was also effective to reduce anthracnose disease severity in vivo when applied as a preventive measure on chili and papaya fruits. This study could be used as a reference for further fruit coating application using nano chitosan as a promising postharvest biocontrol agent to C. gloeosporioides.</p>

scholarly journals ETHYLCELLULOSE FLOATING MICROSPHERES OF ANTIDIABETIC AGENT: IN VITRO AND IN VIVO EVALUATION

2016 ◽  
Vol 9 (1) ◽  
pp. 44 ◽  
Author(s):  
Seema Kohli ◽  
Megha Sharma ◽  
Abhisek Pal
Keyword(s):  
Average Particle Size ◽  
Insulin Dependent Diabetes Mellitus ◽  
Treated Group ◽  
Antidiabetic Activity ◽  
Dependent Diabetes Mellitus ◽  
Average Particle ◽  
In Vivo Evaluation ◽  
Gastro Retentive

Objective: To develop and evaluate floating type gastro-retentive dosage form, appropriate for controlled release of repaglinide (RG) having a narrow therapeutic window.Methods: Repaglinide loaded microspheres (MS) using biological macromolecule ethylcellulose (EC) was prepared by a solvent diffusion-evaporation technique using polyvinyl alcohol (PVA) emulsifier. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). During formulation, various process optimisation parameters studied were stirring speed, the concentration of drug, polymer and emulsifier. Characterization and in vitro evaluation was performed. In vivo antidiabetic activity was performed on alloxan induced diabetic rats followed by histopathological screening.Results: The average particle size was in the range of 174-243 µm. Yield, entrapment and buoyancy of microspheres were 68.4­­-79.8, 58.6-73.1 and 71.8-84.1% respectively. 65.1% release of drug from optimised formulation was obtained which follows first-order kinetics (r2 = 0.989). Optimised formulation treated group shows significant (p<0.01) decrease in glucose level of blood as compared to pure drug treated group during the later hours of study with satisfactory results of histology.Conclusion: The investigation revealed the promising potential of gastro retentive microspheres for delivering RG for the treatment of non-insulin dependent diabetes mellitus (NIDDM).

Hepatocellular Carcinoma Targeting and Pharmacodynamics of Paclitaxel Nanoliposomes Modified by Glycyrrhetinic Acid and Ferric Tetroxide

2021 ◽  
Vol 21 ◽  
Author(s):  
Ling Zhao ◽  
Leyi Liang ◽  
Mimi Guo ◽  
Ming Li ◽  
Xuesong Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Delivery ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Glycyrrhetinic Acid ◽  
Migration And Invasion ◽  
Average Particle ◽  
Hcc Cells

Aims: Research on developing targeted delivery of anticancer drugs for the treatment of hepatocellular carcinoma (HCC) is ongoing. This study aimed at synthesizing nanoliposomes modified by glycyrrhetinic acid (GA) and ferric tetroxide (Fe3O4) for targeted delivery of paclitaxel for selective and specific therapy of HCC. Objective: During this project, GA and Fe3O4 were used to jointly modify the active targeting and magnetic orientation of paclitaxel nanoliposomes for enhanced targeting of HCC to improve the efficacy, while reducing the systemic toxicity and side effects of the drug. Methods: In this study, liposomes were prepared to utilize a thin film dispersion method, in which the average particle size of GA/Fe3O4-PTX-LP was 148.9 ± 2.3 nm, and the average Zeta potential was -23.2 ± 3 mV. Based on the TEM characterization, GA/Fe3O4-PTX-LP is a closed particle with bilayer membranes. In vitro release assessments of the drug indicated that the release of GA/Fe3O4-PTX-LP was sustained. Results: In vitro cell tests have demonstrated that GA/Fe3O 4-PTX-LP can inhibit the proliferation, affect the morphology, migration and invasion, and interfere with the cycle of HCC cells. Uptake tests have confirmed that GA/Fe3O4-PTX-LP can promote the uptake of the drug in HCC cells. Conclusion: In vivo targeting experiments have shown that GA/Fe3O4-PTX-LP has a strong ability to target tumors. In vivo antitumor assessments have proven that GA/Fe3O4-PTX-LP can inhibit tumor growth without obvious toxicity. This project provides a promising nano-targeted drug delivery system for the treatment of HCC.

Appraisal of Nano-lipidic Astaxanthin cum Thermoreversible Gel and its Efficacy in Haloperidol Induced Parkinsonism

2021 ◽  
Vol 18 ◽  
Author(s):  
Deepika Gautam ◽  
Samipta Singh ◽  
Priyanka Maurya ◽  
Manjari Singh ◽  
Sapana Kushwaha ◽  
...  
Keyword(s):  
Average Particle Size ◽  
Radical Scavenging ◽  
Nanostructured Lipid Carriers ◽  
Neuronal Uptake ◽  
Pharmacokinetic Studies ◽  
Average Particle ◽  
In Situ Gel ◽  
Thermoreversible Gel

Background: Parkinsonism has a toxic cascade of neurodegeneration, with akinesia as a major manifestation. Some antioxidants have shown promise against the disease. Astaxanthin is a powerful antioxidant, demonstrates free radical scavenging, and is also a potential neuroprotective agent Objective: To formulate astaxanthin laden nanostructured lipid carriers based thermoreversible gel for better neuronal uptake and better neuronal efficacy. Methods: The method for fabricating astaxanthin-nanostructured lipid carriers (ATX-NLC) was melt-emulsification, and these were optimized using factorial design and further evaluated for diverse parameters. Neurotoxicity was induced in rats by haloperidol. The treated and non-treated rats were then witnessed for their behaviour. TBARs and GSH levels were also determined. Pharmacokinetics was studied via HPLC. Results: The average particle size (by DLS), entrapment efficiency and zeta potential of optimized ATX-NLC were 225.6 ± 3.04 nm, 65.91 ± 1.22 % and -52.64 mV respectively. Astaxanthin release (after 24 h in simulated nasal fluid) from optimized ATX-NLC was 92.5 ± 5.42 %. Its thermo-reversible nasal gel (ATX-NLC in-situ gel) was prepared using poloxamer-127. The obtained gel showed in-vivo betterment in the behaviour of animals when studied using rotarod and akinesia test. Pharmacokinetic studies showed better availability of astaxanthin in the brain on the rats treated with ATX-NLC in-situ gel as compared to those treated with ATX-in-situ gel. Conclusion: Astaxanthin loaded lipidic nanoparticulate gel can be a hopeful adjuvant therapy for Parkinsonism and holds scope for future studies.

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