A New Calcium Oral Controlled-Release System Based on Zeolite for 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.

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Controlled Release of Endothelial Cell Growth Factor from Chitosan-Albumin Microspheres for Localized Angiogenesis: In Vitro and in Vivo Studies

Artificial Cells Blood Substitutes and Biotechnology ◽

10.3109/10731199609117438 ◽

1996 ◽

Vol 24 (3) ◽

pp. 257-271 ◽

Cited By ~ 46

Author(s):

Y. Murat Elçin ◽

Vivek Dixit ◽

Gary Gitnick

Keyword(s):

Endothelial Cell ◽

Controlled Release ◽

Growth Factor ◽

Cell Growth ◽

In Vivo Studies ◽

Albumin Microspheres ◽

Endothelial Cell Growth Factor ◽

Endothelial Cell Growth

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

Current Drug Delivery ◽

10.2174/1567201818666210203180853 ◽

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.

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

10.21203/rs.3.rs-17757/v1 ◽

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.

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In vitro Controlled Release of two new Tuberculocidal Adamantane Aminoethers from Solid Pharmaceutical Formulations (II)

Drug Research ◽

10.1055/s-0043-114012 ◽

2017 ◽

Vol 67 (11) ◽

pp. 653-660 ◽

Cited By ~ 6

Author(s):

Marilena Vlachou ◽

Angeliki Siamidi ◽

Dimitrios Spaneas ◽

Dimitrios Lentzos ◽

Polixeni Ladia ◽

...

Keyword(s):

Controlled Release ◽

In Vitro Release ◽

Pharmaceutical Formulations ◽

Adamantane Derivative ◽

In Vivo Studies ◽

Matrix Tablet ◽

The Us ◽

Vitro Release

AbstractThe aim of the present investigation was to develop matrix tablet formulations for the in vitro controlled release of two new tuberculocidal adamantane aminoethers (compounds III and IV), congeneric to the adamantane derivative SQ109, which is in final clinical trials, and aminoethers (I) and (II), using carefully selected excipients, such as polyvinylpyrrolidone, sodium alginate and lactose. The tablets were prepared using the direct compression method and dissolution experiments were conducted using the US Pharmacopoeia type II apparatus (paddle method) in gastric and intestinal fluids. The results suggest that both analogues, albeit more lipophilic than SQ109, and aminoethers (I) and (II), have the requisite in vitro release characteristics for oral administration. In conclusion, these formulations merit further assessment by conducting in vivo studies, at a later stage.

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In vitro Controlled Release from Solid Pharmaceutical Formulations of two new Adamantane Aminoethers with Antitubercular Activity (I).

Drug Research ◽

10.1055/s-0042-121491 ◽

2017 ◽

Vol 67 (08) ◽

pp. 447-450 ◽

Cited By ~ 5

Author(s):

Marilena Vlachou ◽

Angeliki Siamidi ◽

Evanthia Diamantidi ◽

Alexandra Iliopoulou ◽

Ioannis Papanastasiou ◽

...

Keyword(s):

Controlled Release ◽

In Vitro Release ◽

Antitubercular Activity ◽

Pharmaceutical Formulations ◽

Adamantane Derivative ◽

In Vivo Studies ◽

Matrix Tablet ◽

The Us

AbstractThe aim of the present investigation was to develop matrix tablet formulations for the in vitro controlled release of 2 new tuberculocidal adamantane aminoethers (compounds I and II), congeneric to the adamantane derivative SQ109, which is in final clinical trials, using carefully selected excipients, such as polyvinylpyrrolidone, sodium alginate and lactose. The tablets were prepared using the direct compression method and dissolution experiments were conducted using the US Pharmacopoeia type II apparatus (paddle method) in gastric and intestinal fluids. The results confirm that both analogues, albeit more lipophilic than SQ109, showed satisfactory in vitro release characteristics from solid pharmaceutical formulations. In conclusion, these formulations merit further assessment by conducting in the future bioavailability in vivo studies.

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.1164 ◽

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.

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

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x15666180612090816 ◽

2018 ◽

Vol 16 (1) ◽

pp. 78-91 ◽

Cited By ~ 5

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.

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Review on Adverse effects or side effects of Remdisivir

Research Journal of Pharmacology and Pharmacodynamics ◽

10.52711/2321-5836.2021.00030 ◽

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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