scholarly journals Pharmaceutical Characterization and In Vivo Evaluation of Orlistat Formulations Prepared by the Supercritical Melt-Adsorption Method Using Carbon Dioxide: Effects of Mesoporous Silica Type

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 333 ◽  
Author(s):  
Heejun Park ◽  
Kwang-Ho Cha ◽  
Seung Hyeon Hong ◽  
Sharif Md Abuzar ◽  
Seungyeol Lee ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Particle Size ◽  
Side Effects ◽  
Mesoporous Silica ◽  
Dissolution Rate ◽  
Lipase Activity ◽  
Pore Volume ◽  
In Vivo Studies

Orlistat, an anti-obesity drug, has two critical issues—the first is its low efficacy due to low water solubility and the second is side effects such as oily spotting due to its lipase inhibition. The present study was designed to propose a solution using a formulation with mesoporous silica to simultaneously overcome two issues. Orlistat was loaded onto mesoporous silica by the supercritical melt-adsorption (SCMA) method, using carbon dioxide (CO2). Various types of mesoporous silica were used as adsorbents, and the effects of the pore volume, diameter and particle size of mesoporous silica on the pharmaceutical characteristics were evaluated by various solid-state characterization methods and in vitro and in vivo studies in relation to pharmacological efficacy and the improvement of side effects. The results showed that the pore volume and diameter determine loadable drug amount inside pores and crystallinity. The dissolution was significantly influenced by crystallinity, pore diameter and particle size, and the inhibition of lipase activity was in proportion to the dissolution rate. In vivo studies revealed that the serum triglyceride (TG) concentration was significantly decreased in the group administered amorphous orlistat-loaded Neuisilin®UFL2 with the highest in vitro dissolution rate and lipase activity inhibition in comparison to the commercial product. Furthermore, oily spotting tests in rats revealed that undigested oil was adsorbed onto mesoporous silica after orlistat was released in the gastro-intestinal tract, and it correlated with in vitro result that oil adsorption capacity was dependent on the surface area of empty mesoporous silica. Therefore, it was concluded that mesoporous silica type plays a major role in determining the pharmaceutical characteristics of orlistat formulation prepared using SCMA with CO2 for improving the low solubility and overcoming the side effects.

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

Pomegranate, its Components and Modern Deliverable Formulations as Potential Botanicals in the Prevention and Treatment of Various Cancers

2021 ◽  
Vol 18 ◽  
Author(s):  
Laila Hussein ◽  
Mostafa Gouda ◽  
Harpal S. Buttar
Keyword(s):  
Side Effects ◽  
Biological Tissues ◽  
Pomegranate Juice ◽  
In Vivo Studies ◽  
Lifestyle Modifications ◽  
Cellular Mechanisms ◽  
Double Blind ◽  
Prevention And Treatment

Abstract: Cancer is a global multifactorial disease consisting of over 200 types of cancers. It is well recognized that primary prevention is an effective way to fight cancers by using natural polyphenolic anticancer foods, vegetables and fruits, avoiding exposure to carcinogenic environment, smoking cessation, and through lifestyle modifications. The present review provides up to date information on the effects and functions of pomegranate juice and its bioactive components on the most widespread six cancer types. Pomegranate contains important polyphenolic compounds such as ellagitannins and punicalagin, with strong antioxidant ability for scavenging free radicals and producing metal-chelates in the biological tissues. The in vitro and in vivo studies suggests that antioxidant and anti-inflammation properties of pomegranate constitute have major antimutagenic and antiproliferative activities for regulating gene expression, modulating cellular mechanisms, and limiting the ability of cancers to metastasize. A limited number of clinical studies have suggested that pomegranate ingredients have the potential for the prevention and treatment of cancer, especially colorectal and prostate cancer. In cancer therapy, it remains a clinical dilemma to hit the right target without inducing side effects. The costly anticancer chemotherapies are often associated with drug resistance and serious side effects in vital organs, and noncancerous neighboring cells. It appears that the pomegranate based phytotherapies would be affordable and cost-effective for next generation non-pharmacologic anticancer remedies with lesser side effects. However, well-designed, randomized, double-blind, and multi-center studies are needed to establish the long-term safety, efficacy and dose schedules for orally deliverable pomegranate formulations.

scholarly journals Novel T7-modified pH-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer

2020 ◽  
Author(s):  
Lian Deng ◽  
Xiongjie Zhu ◽  
Zhongjian Yu ◽  
Ying Li ◽  
Lingyu Qin ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Side Effects ◽  
High Efficiency ◽  
In Vivo Studies ◽  
Ph Responsive ◽  
Therapeutic Platform ◽  
Multiple Drugs ◽  
Esophageal Cancer Cells

Abstract Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side effects. Nanomedicines have increasingly attracted attention because of their good biological safety, targeting and high-efficiency loading of multiple drugs. Herein, we have developed a pH-responsive nanocarrier that has high affinity for the transferrin receptor, which is overexpressed by tumor cells. The system is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor, and exerts a synergistic anti-tumor effect, and T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively. In vitro and in vivo studies showed that improved anti-tumor efficacy could be obtained by loading docetaxel and curcumin into the T7-modified nanocarrierwithout obvious toxicity or side effects, compared to drug without nanocarrier. Furthermore, the nanocarriers conjugated with T7 short peptides were more readily taken up by esophageal cancer cells compared with normal cells.Together, our findings indicate that the materials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.

scholarly journals DEVELOPMENT OF RITONAVIR LOADED NANOPARTICLES: IN VITRO AND IN VIVO CHARACTERIZATION

2018 ◽  
Vol 11 (3) ◽  
pp. 284
Author(s):  
Pravin S Patil ◽  
Shashikant C Dhawale
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Dissolution Rate ◽  
Drug Carrier ◽  
Entrapment Efficiency ◽  
Significant Rise ◽  
Scanning Calorimetry ◽  
In Vitro Drug Release

 Objective: The purpose of the present investigation was to develop a nanosuspension to improve dissolution rate and oral bioavailability of ritonavir.Methods: Extended-release ritonavir loaded nanoparticles were prepared using the polymeric system by nanoprecipitation technique. Further, the effect of Eudragit RL100 (polymeric matrix) and polyvinyl alcohol (surfactant) was investigated on particle size and distribution, drug content, entrapment efficiency, and in vitro drug release from nanosuspension where a strong influence of polymeric contents was observed. Drug-excipient compatibility and amorphous nature of drug in prepared nanoparticles were confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies, respectively.Results: Hydrophobic portions of Eudragit RL100 could result in enhanced encapsulation efficiency. However, increase in polymer and surfactant contents lead to enlarged particle size proportionately as confirmed by transmission electron microscopy. Nanosuspension showed a significant rise in dissolution rate with complete in vitro drug release as well as higher bioavailability in rats compared to the pure drug.Conclusion: The nanoprecipitation technique used in present research could be further explored for the development of different antiretroviral drug carrier therapeutics.

scholarly journals Preparation and preclinical evaluation of aceclofenac loaded pectinate mucoadhesive microspheres

2012 ◽  
Vol 2 (1) ◽  
pp. 8 ◽  
Author(s):  
Santanu Chakraborty ◽  
Priyanka Nayak ◽  
Bala Murali Krishna ◽  
Madhusmruti Khandai ◽  
Ashoke Kumar Ghosh
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Polymer Concentration ◽  
Research Work ◽  
In Vivo Studies ◽  
Systemic Absorption ◽  
Cross Linking ◽  
Significant Difference

The aim of the present research work was to fabricate aceclofenac loaded pectinate microspheres by ionic gelation method and evaluate the effect of different cross-linking agents and polymer concentration on particle size, encapsulation efficacy and drug release behavior. It was also investigated that whether this pectinate dosage form was able to target the drug release in intestinal region and prevent the different side effect associated with the drug in stomach or not. It was observed that particle size, encapsulation efficacy and in vitro drug release were largely depended on polymer concentration and cross-linking agents. It was also observed that pectinate microspheres showed excellent pH depended mucoadhesive properties and they were able to restrict the drug release in stomach. <em>In vitro</em> drug release study showed that alminium-pectinate microspheres have more sustaining property as compared to barium-pectinate microspheres. Holm-Sidak multiple comparison analysis suggested a significant difference in measured t<sub>50%</sub> values among all the formulations with same cross-linking agent. In vivo studies revealed that the anti inflammatory and analgesic effects induced by pectinate microspheres were significantly high and prolonged as compared to pure drug. So, pectinate microspheres can be an excellent carrier for targeting the delivery of aceclofenac as well as help in improving the patient compliance by prolonging the systemic absorption.

scholarly journals A New Calcium Oral Controlled-Release System Based on Zeolite for Prevention of Osteoporosis

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2467 ◽  
Author(s):  
Angela Fabiano ◽  
Anna Maria Piras ◽  
Vincenzo Calderone ◽  
Lara Testai ◽  
Lorenzo Flori ◽  
...  
Keyword(s):  
Controlled Release ◽  
Side Effects ◽  
Calcium Ions ◽  
Rank Order ◽  
In Vivo Studies ◽  
Current Therapy ◽  
Effective Prevention ◽  
Prevention Of Osteoporosis

Osteoporosis, a systemic skeleton disease, can be prevented by increasing calcium levels in serum via administration of calcium salts. However, traditional calcium-based formulations have not appeared to be effective, hence the purpose of the present work has been to prepare and test in vitro/vivo a formulation able to gradually release calcium during transit over the GI tract, thus increasing bioavailability and reducing daily dose, and hence, side effects. Calcium controlled-release granules based on zeolite and Precirol® were prepared. In the best case, represented by granules sized 1.2 mm, containing 20% Precirol®, 19% zeolite, 60% calcium (granule), the release lasted ≈6 h. The release is controlled by diffusion of calcium ions through the aqueous channels forming within granules, once these come into contact with physiological fluids. Such a diffusion is hindered by the interaction of calcium ions with the negatively charged surface of the zeolite. Ovariectomy was used to make rats osteopenic. For in vivo studies, rats were divided into the following groups. Sham: not treated; ova: ovariectomized (ova); CaCl2 1.0 g: ova, treated with 1.0 g/die Ca2+; CaCl2 0.5 g: ova, treated with 0.5 g/die Ca2+; granule 1.0 g, or granule 0.5 g: ova, treated with granules equivalent to 1.0 g/die or 0.5 g/die Ca2+ in humans. Ca2+ amounts in femur bone and bone marrow, femur mechanical characteristics, and femur medullary canalicule diameter were measured and the same efficacy rank order was obtained: ova < CaCl2 0.5 g < CaCl2 1.0 g < granule 0.5 g ≈ granule 1.0 g ≈ sham. The results show promise of an effective prevention of osteoporosis, based on a controlled-rate administration of a calcium dose half that administered by the current therapy, with reduced side effects.

scholarly journals SCIDOT-28. TARGETED NANOPARTICLES FOR IMPROVED DRUG DELIVERY TO MEDULLOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi277-vi277
Author(s):  
Joelle P Straehla ◽  
Natalie Boehnke ◽  
Tamara G Dacoba ◽  
Paula T Hammond
Keyword(s):  
Drug Delivery ◽  
Endothelial Cells ◽  
Side Effects ◽  
Tumor Cells ◽  
Chemical Engineering ◽  
Xenograft Model ◽  
In Vivo Studies ◽  
Layer By Layer

Abstract Platinum-based agents remain a key component of therapy for children with medulloblastoma, despite significant systemic side effects and only modest blood-brain barrier (BBB) penetration. Cisplatin has a cerebrospinal fluid-to-plasma ratio <5% and dose-limiting side effects of nephrotoxicity, ototoxicity, and myelosuppression. Improving delivery of cisplatin across the BBB and selectively accumulating in tumors could improve its therapeutic index. To this end, we are leveraging chemical engineering techniques to rationally design cisplatin nanoparticles (NPs) to cross the BBB and preferentially enter medulloblastoma tumor cells. Using the layer-by-layer (LbL) platform to ‘wrap’ polyelectrolytes around a NP core by iterative electrostatic adsorption, we screened six negatively charged polypeptide and polysaccharide outer layers in medulloblastoma cell lines. Poly-L-aspartic acid (PLD) layered NPs had significant accumulation in tumor cells after 24 hours incubation, with an uptake index of 18±4 over unlayered control NPs. Next, we generated propargyl-functionalized PLD and used click chemistry to covalently conjugate the BBB shuttle ligands glutathione, angiopep-2, and transferrin, which have been shown to mediate transcytosis across brain endothelial cells. PLD layered NPs functionalized with angiopep-2 and transferrin had enhanced uptake in medulloblastoma tumor cells and NPs functionalized with glutathione were non-inferior to PLD layered NPs. After incubation with endothelial cells in vitro, all three BBB shuttle ligands enhanced uptake of PLD layered NPs over unlayered and non-functionalized control NPs. We then incorporated cisplatin into the nanoparticle core of this platform. Cisplatin-loaded NPs with PLD layering and ligand functionalization were more effective than free cisplatin as measured by IC50 over 72 hours in culture, and led to faster apoptosis as assessed by flow cytometry with annexin V and propidium iodide staining. In summary, functionalized nanoparticles are a promising platform to modulate drug delivery to medulloblastoma. In vivo studies using an orthotopic xenograft model are underway to investigate biodistribution, efficacy, and toxicity.

Ursolic and Oleanolic Acids as Potential Anticancer Agents Acting in the Gastrointestinal Tract

2018 ◽  
Vol 16 (1) ◽  
pp. 78-91 ◽  
Author(s):  
Mateusz Pięt ◽  
Roman Paduch
Keyword(s):  
Gastrointestinal Tract ◽  
Side Effects ◽  
Anticancer Agents ◽  
In Vivo Studies ◽  
Pentacyclic Triterpenoids ◽  
Liver Cancers ◽  
Anti Cancer ◽  
Tumorigenic Activity

Background:Cancer is one of the main causes of death worldwide. Contemporary therapies, including chemo- and radiotherapy, are burdened with severe side effects. Thus, there exists an urgent need to develop therapies that would be less devastating to the patient’s body. Such novel approaches can be based on the anti-tumorigenic activity of particular compounds or may involve sensitizing cells to chemotherapy and radiotherapy or reducing the side-effects of regular treatment.Objective:Natural-derived compounds are becoming more and more popular in cancer research. Examples of such substances are Ursolic Acid (UA) and Oleanolic Acid (OA), plant-derived pentacyclic triterpenoids which possess numerous beneficial properties, including anti-tumorigenic activity.Results:In recent years, ursolic and oleanolic acids have been demonstrated to exert a range of anticancer effects on various types of tumors. These compounds inhibit the viability and proliferation of cancer cells, prevent their migration and metastasis and induce their apoptosis. Both in vitro and in vivo studies indicate that UA and OA are promising anti-cancer agents that can prevent carcinogenesis at each step. Furthermore, cancers at all stages are susceptible to the activity of these compounds. </P><P> Neoplasms that are formed in the gastrointestinal tract, i.e. gastric, colorectal, pancreatic, and liver cancers, are among the most common and most lethal malignancies. Their localization in the digestive system, however, facilitates the action of orally-administered (potential) anti-cancer agents, making chemopreventive drugs more accessible.In this paper, the anti-tumorigenic effect of ursolic and oleanolic acids on gastric, colon, pancreatic, and liver cancers, as well as the mechanisms underlying this process, are presented.

Nanoliposomal Encapsulation Enhances In Vivo Anti-Tumor Activity of Niclosamide against Melanoma

2019 ◽  
Vol 19 (13) ◽  
pp. 1618-1626 ◽  
Author(s):  
Mahdi Hatamipour ◽  
Mahmoud R. Jaafari ◽  
Amir A. Momtazi-Borojeni ◽  
Mahin Ramezani ◽  
Amirhossein Sahebkar
Keyword(s):  
Particle Size ◽  
Aqueous Solubility ◽  
In Vivo Studies ◽  
Size Analysis ◽  
Parasitic Infections ◽  
B16f10 Melanoma ◽  
Melanoma Tumor ◽  
Anti Tumor Activity

Background: Niclosamide is an FDA-approved and old anti-helminthic drug used to treat parasitic infections. Recent studies have shown that niclosamide has broad anti-tumor effects relevant to the treatment of cancer. However, this drug has a low aqueous solubility hindering its systemic use. Herein, we report the preparation and characterization of niclosamide nanoliposomes and their in vivo anti-tumor effects. Methods: Nanoliposomes were prepared using thin-film method and the drug was encapsulated with a remote loading method. The nanoliposomes were investigated by the observation of morphology, analysis of particle size and zeta potential. Additionally, qualitative and quantitative analyses were performed using HPLC. We assessed the in vitro cytotoxicity of the nanoliposomal niclosamide on B16F10 melanoma cells. Inhibition of tumor growth was investigated in C57BL/6 mice bearing B16F0 melanoma cancer. Results: Analytical results indicated that the nanoliposomal system is a homogeneous and stable colloidal dispersion of niclosamide particles. Atomic force microscopy images and particle size analysis revealed that all niclosamide particles had a spherical shape with a diameter of approximately 108nm. According to in vitro and in vivo studies, nanoliposomal niclosamide exhibited a better anti-tumor activity against B16F10 melanoma tumor compared with free niclosamide. Conclusion: Nanoliposomal encapsulation enhanced the aqueous solubility of niclosamide and improved its anti-tumor properties.

Review on Adverse effects or side effects of Remdisivir

2021 ◽  
pp. 162-166
Author(s):  
Ganesh G. Dhakad ◽  
Rohit V. Patil ◽  
Tejas I. Chaudhari ◽  
Paresh A. Patil.
Keyword(s):  
Side Effects ◽  
Ebola Virus ◽  
Clinical Symptoms ◽  
Virus Disease ◽  
Clinical Status ◽  
World Health ◽  
In Vivo Studies ◽  
Rater Agreement

In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100–200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020–2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population. But the remdesivir is also harmful for the people because of it can have some side effects such as mentioned in the following information. There are so many type of disease started form the treatment of COVID-19 with the Remdesivir that also mentioned in the following review paper.

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