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In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of paclitaxel (Taxol®), ...while maximizing the proven antineoplastic activity of the drug against many solid tumors. Hence, different types of nanocarriers have been employed to improve the efficacy, safety, physicochemical properties and pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the unique drug that is marketed in three different nanoplatforms for its parenteral delivery: polymeric nanoparticles (Abraxane®), liposomes (Lipusu®), and polymeric micelles (Genexol®, Nanoxel® and Paclical®). Indeed, a fourth nanocarrier might be available soon, because phase III studies of Opaxio™, a polymeric-conjugated, are near completion. Furthermore, other several nanoformulations are currently in various stages of clinical trials. Therefore, it is only through the critical analysis of clinical evidence from these studies that we can get a more concrete idea of what has been achieved with pharmaceutical nanotechnology so far.
This review attempts to summarize current information available regarding the clinical status and the physicochemical characteristic of different nanocarriers for paclitaxel delivery in cancer therapy. We present an overview of the preclinical and clinical data of these systems including their pharmacokinetics, dose and administration, adverse events and clinical efficacy.
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Nanoscale materials have contributed changing the way biomedical researchers address the biological and therapeutic limitations of conventional drugs and diagnostic agents. Thanks to ...a plethora of different materials and synthetic routes, particulate carriers can be designed to modify the half-life of compounds, alter their biodistribution and control the drug release profile, eventually providing an overall clinical benefit to patients. While around 50 nanoformulations (excluding biologics) are already on the market, several challenges still withhold them from unlocking their full translational potential. This review discusses the advantages and current hurdles in the use of nanopharmaceuticals, and describes the most important nanotechnological approaches which have been investigated so far. A focus is given on the record of clinical success and failures and current clinical trends. In an effort to identify opportunities and problems associated with each specific nanosystem, this manuscript underlines the need of a more product-oriented research, that can foster the progress of nanomedicines to the clinic.
The use of nanocarriers is gaining weight in the world of drug delivery, especially in cancer treatment. They allow an increase in the therapeutic efficacy of the drugs in the tumor, but they also ...can be used to improve their specificity and to prolong their mean circulation half-life. This review focuses on the latest discoveries in drug nanocarriers and their use in cancer treatment. Display omitted
Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects.
Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that mainly deliver chemotherapeutic agents to molecular targets overexpressed on the surface of tumor cells. In particular, we offer a detailed description of different cytotoxic drug carriers, such as liposomes, carbon nanotubes, dendrimers, polymeric micelles, polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers, respectively, emphasizing those that have received FDA approval or are part of the most important clinical studies up to date. These drug carriers not only transport the chemotherapeutic agents to tumors, avoiding normal tissues and reducing toxicity in the rest of the body, but also protect cytotoxic drugs from degradation, increase the half-life, payload and solubility of cytotoxic agents and reduce renal clearance. Despite the many advantages of all the anticancer drug carriers analyzed, only a few of them have reached the FDA approval, in particular, two polymer–protein conjugates, five liposomal formulations and one polymeric nanoparticle are available in the market, in contrast to the sixteen FDA approval of monoclonal antibodies. However, there are numerous clinical trials in progress of polymer–protein and polymer–drug conjugates, liposomal formulations, including immunoliposomes, polymeric micelles and polymeric nanoparticles. Regarding carbon nanotubes or dendrimers, there are no FDA approvals or clinical trials in process up to date due to their unresolved toxicity. Moreover, we analyze in detail the more promising and advanced preclinical studies of the particular case of polymeric nanoparticles as carriers of different cytotoxic agents to active and passive tumor targeting published in the last 5years, since they have a huge potential in cancer therapy, being one of the most widely studied nano-platforms in this field in the last years. The interest that these formulations have recently achieved is stressed by the fact that 90% of the papers based on cancer therapeutics with polymeric nanoparticles have been published in the last 6years (PubMed search).
Various NCDs with antimicrobial, anticancer and neurodegenerative drug delivery applications. a) Pleurotus species, b) Hylocereus undatus, c) Curcuma longa L., d) Manilkara zapota (L.) P. Royen, e) ...Banana leaf, f) Carica papaya, g) Ocimum Sanctum, h) Foeniculum vulgare Mill seeds, i) Azadirachta indica, j) Aloe vera (L.) Burm.f.
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•The source and rationale behind natural carbon quantum dots (NCDs) are carefully discussed.•The various synthesis method and their merits have been summarized.•The optical properties and toxicological profile of NCDs are highlighted.•The drug delivery applications of NCDs are detailed.•The clinical status of NCDs are presented.
Natural carbon based quantum dots (NCDs) are an emerging class of nanomaterials in the carbon family. NCDs have gained immense acclamation among researchers because of their abundance, eco-friendly nature, aqueous solubility, the diverse functionality and biocompatibility when compared to other conventional carbon quantum dots (CDs).The presence of different functional groups on the surface of NCDs such as thiol, carboxyl, hydroxyl, etc., provides improved quantum yield, physicochemical and optical properties which promote bioimaging, sensing, and drug delivery. This review provides comprehensive knowledge about NCDs for drug delivery applications by outlining the source and rationale behind NCDs, different routes of synthesis of NCDs and the merits of adopting each method. Detailed information regarding the mechanism behind the optical properties, toxicological profile including biosafety and biodistribution of NCDs that are favourable for drug delivery are discussed. The drug delivery applications of NCDs particularly as sensing and real-time tracing probe, antimicrobial, anticancer, neurodegenerative agents are reviewed. The clinical aspects of NCDs are also reviewed as an initiative to strengthen the case of NCDs as potent drug delivery agents.
Bladder cancer is the 10th most commonly occurring malignancy worldwide with a 75% of 5-year survival rate, while it ranks 13th among the deaths occurring due to cancer. The majority of bladder ...cancer cases are diagnosed at an early stage and 70% are of non-invasive grade. However, 70% of these cases develop chemoresistance and progress to the muscle invasive stage. Conventional chemotherapy treatments are unsuccessful in curbing chemoresistance, bladder cancer progression while having an adverse side effect, which is mainly due to off-target drug distribution. Therefore, new drug delivery strategies, new therapeutics and therapies or their combination are being explored to develop better treatments. In this regard, nanotechnology has shown promise in the targeted delivery of therapeutics to bladder cancer cells. This review discusses the recent discovery of new therapeutics (chemotherapeutics, immunotherapeutic, and gene therapies), recent developments in the delivery of therapeutics using nano drug delivery systems, and the combination treatments with FDA-approved therapies, i.e., hyperthermia and photodynamic therapy. We also discussed the potential of other novel drug delivery systems that are minimally explored in bladder cancer. Lastly, we discussed the clinical status of therapeutics and therapies for bladder cancer. Overall, this review can provide a summary of available treatments for bladder cancer, and also provide opportunities for further development of drug delivery systems for better management of bladder cancer.
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Detection of Trichomoniasis in cattle in Nineveh province Wasan A. Alobaidii; Qaes T. Alobaidii; Sadam D. Hassan
Al-mağallaẗ al-ʻirāqiyyaẗ li-l-ʻulūm al-bayṭariyyaẗ/Iraqi journal of veterinary sciences,
12/2021, Letnik:
35, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The current study was conducted on the detection of Tritrichomonas foetus in vaginal mucus of infected cows using conventional polymerase chain reaction technique (cPCR) in Nineveh province, Iraq. A ...total of 87 vaginal mucus samples were collected randomly from the vagina of Heifer cows of different ages (2-4, >4-6, >6 years old) and stages of pregnancy with different clinical status (early embryonic death, pyometra, abortion and healthy animals once) by washing cow’s vagina using artificial insemination pipette, DNA extraction of T. foetus was done from vaginal mucus samples, cPCR was attempt using TFR3 and TFR4 primers, Results indicated that 11 cows (12.6 %) were positive for T. foetus. The clinical status of cows demonstrated statistically significant (P<0.05) a higher percentage of Early Embryonic Death at (6.9%) compared to pyometra, abortion, and healthy cows. Furthermore, the percentage of T. foetusinfection was significantly (P<0.05) elevated among cows (>2-4 years old) at (8%) compared to (>4-6 years old) and (>6 years old) cows. This study concluded that T. foetusinfection was an elevated percentage of infection in cows with early embryonic death and in cows (>2-4) years old. This study is the first detected T. foetus in cattle in Nineveh province.
•A randomized clinical trial was conducted on patients hospitalized with COVID-19.•The patient's clinical status was assessed daily on an 8-point ordinal scale.•Infliximab accelerated improvement and ...reduced deterioration of clinical status.•Abatacept was also beneficial.•Cenicriviroc was not beneficial.
A randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the efficacy of infliximab, abatacept, and cenicriviroc in treating patients hospitalized with COVID-19. The patient's clinical status was assessed daily on an 8-point ordinal scale. We evaluated the totality of evidence on the efficacy of the 3 immunomodulators by considering all possible changes in the clinical status of each patient over time. We demonstrated that infliximab accelerated improvement and reduced deterioration of clinical status when added to standard of care. There was also evidence for the benefit of abatacept. There was no evidence for the benefit of cenicriviroc.
•We investigated the factorial structure and measurement invariance of the Child-PARQ (short form).•Findings confirmed the original four-factor model in a Romanian sample of youths.•The scale ...assesses approximately the same latent constructs across age, gender, clinical status, parents, and time.•The scale demonstrated adequate criterion validity with internalizing and externalizing symptoms.•The Child-PARQ (short form) is a valuable tool with acceptable psychometric properties.
This study aimed to investigate the factorial structure and measurement invariance of the Romanian version of the Child Parental Acceptance-Rejection Questionnaire- Short Form (Child-PARQ, short form) across parents, age, gender, clinical status, and time. Participants were 1,237 youths (community sample: N = 1,033; clinical sample: N = 204) aged 11–18 years old. The analysis was conducted using RStudio. The factorial structure of the scale was assessed using confirmatory factor analysis, and measurement invariance was examined via multi-group confirmatory factor analysis. Results confirmed the original four-factor model for both the PARQ-Mother and the PARQ-Father. For the PARQ-Mother, we found measurement invariance across gender and time, and partial measurement invariance across age and clinical status. Regarding the PARQ-Father, we confirmed measurement invariance across gender, age, and time, and partial measurement invariance across clinical status. Finally, we demonstrated measurement invariance across the PARQ-Mother and the PARQ-Father. Criterion validity was also demonstrated by finding significant associations with internalizing and externalizing symptoms, as measured by the Strengths and Difficulties Questionnaire (SDQ). Overall, the present findings suggest that the Child-PARQ (short form) is a valuable tool with acceptable psychometric properties for assessing perceived parental acceptance-rejection in preadolescents and adolescents.
Autophagy, a programmed cell-lysis mechanism, holds significant promise in the prevention and treatment of a wide range of conditions, including cancer, Alzheimer's, and Parkinson's disease. The ...successful utilization of autophagy modulation for therapeutic purposes hinges upon accurately determining the role of autophagy in disease progression, whether it acts as a cytotoxic or cytoprotective factor. This critical knowledge empowers scientists to effectively manipulate tumor sensitivity to anti-cancer therapies through autophagy modulation, while also circumventing drug resistance. However, conventional therapies face limitations such as low bioavailability, poor solubility, and a lack of controlled release mechanisms, hindering their clinical applicability. In this regard, innovative nanoplatforms including organic and inorganic systems have emerged as promising solutions to offer stimuli-responsive, theranostic-controlled drug delivery systems with active targeting and improved solubility. The review article explores a variety of organic nanoplatforms, such as lipid-based, polymer-based, and DNA-based systems, which incorporate autophagy-inhibiting drugs like hydroxychloroquine. By inhibiting the glycolytic pathway and depriving cells of essential nutrients, these platforms exhibit tumor-suppressive effects in advanced forms of cancer such as leukemia, colon cancer, and glioblastoma. Furthermore, metal-based, metal-oxide-based, silica-based, and quantum dot-based nanoplatforms selectively induce autophagy in tumors, leading to extensive cancer cell destruction. Additionally, this article discusses the current clinical status of autophagy-modulating drugs for cancer therapy with valuable insights of progress and potential of such approaches.
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•Dual-role of autophagy in both tumor suppression and tumor activation.•Organic nanoplatforms for cancer therapy and reversal of drug resistance by autophagy inhibition.•Inorganic nanoparticles for cancer suppression by selective autophagy induction in tumor.
Bioimpedance analysis is a noninvasive, low cost and a commonly used approach for body composition measurements and assessment of clinical condition. There are a variety of methods applied for ...interpretation of measured bioimpedance data and a wide range of utilizations of bioimpedance in body composition estimation and evaluation of clinical status. This paper reviews the main concepts of bioimpedance measurement techniques including the frequency based, the allocation based, bioimpedance vector analysis and the real time bioimpedance analysis systems. Commonly used prediction equations for body composition assessment and influence of anthropometric measurements, gender, ethnic groups, postures, measurements protocols and electrode artifacts in estimated values are also discussed. In addition, this paper also contributes to the deliberations of bioimpedance analysis assessment of abnormal loss in lean body mass and unbalanced shift in body fluids and to the summary of diagnostic usage in different kinds of conditions such as cardiac, pulmonary, renal, and neural and infection diseases.
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