1. Anticancer Drugs: Recent Strategies to Improve Stability Profile ... - NCBI
Aug 25, 2022 · This approach allows overcoming several drawbacks, including poor water solubility, chemical instability, inadequate oral or local absorption, ...
In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low ...
2. Nanocarrier for Poorly Water-Soluble Anticancer Drugs—Barriers ... - NCBI
Apr 2, 2014 · In general, poor PWSAD encapsulation can be contributed by several factors such as ... Poor aqueous solubility of drugs has been a common but ...
Many existing chemotherapeutic drugs, repurposed drugs and newly developed small-molecule anticancer compounds have high lipophilicity and low water-solubility. Currently, these poorly water-soluble anticancer drugs (PWSAD) are generally solubilized using ...
3. Bioavailability Enhancement Techniques for Poorly Aqueous ...
Pharmaceutical compounds with poor water solubility can intensely decrease output in drug discovery and development. A “good compound” must reach the target ...
See AlsoWhich Mode Of Assessment Provides A Better Opportunity For Reflection?Which Lists Three Units Of An Organ System In Order From The Simplest To The Most Complex? Red Blood Cell → Heart → Tissue Skeleton → Bone → Bone Cell Muscle Cell → Muscle Tissue → Stomach Lung Tissue → Lung → Circulatory SystemKonversikanbilanganbiner 110110 Ke Dalam Bentuk Heksadesimal.12.3 Fl. Oz. → Mm3The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry’s screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.
4. Development of o-aminobenzamide salt derivatives for improving water ...
Jun 19, 2023 · Firstly, F8·2CH3SO2OH has poor water solubility, and it is an oily, non-salt crystal. And F8·2HBr has strong hygroscopicity, it changed from ...
Background: Gastric cancer is one of the cancers with wide incidence, difficult treatment and high mortality in the world, especially in Asia and Africa. In our previous work, a novel o-aminobenzamide analogue F8 was identified as an early preclinical candidate for treatment of undifferentiated gastric cancer (IC50 of 0.26 μM for HGC-27). However, the poor water solubility of compound F8 prevents its further progress in preclinical studies.Aim: To improve the water solubility and drug-likeness of F8 via salt formation.Method: Different acids and F8 were reacted to obtain different salt forms. Physicochemical property screening, pharmacokinetic property research, and antitumor biological activity evaluation in vitro and in vivo were used to obtain the optimal salt form with the best druggability.Results: our continuous efforts have finally confirmed F8·2HCl as the optimal salt form with maintained in vitro antitumor activity, improved water solubility and pharmacokinetic properties. Importantly, the F8·2HCl displayed superior in vivo antitumor efficacy (TGI of 70.1% in 75 mg/kg) in HGC-27 xenograft model. The further immunohistochemical analysis revealed that F8·2HCl exerts an antitumor effect through the regulation of cell cycle-related protein (CDK2 and p21), apoptosis-related protein Cleaved Caspase-3, proliferation marker Ki67, and cell adhesion molecule E-cadherin. In addition, F8·2HCl showed acceptable safety in the in vivo acute toxicity assay.Conclusion: Salting is ...
5. Nanomaterials for cancer therapy: current progress and perspectives
May 31, 2021 · Poor water solubility and toxicity are two drawbacks of CNTs. Many studies on surface functionalization and material modifications have been ...
Cancer is a disease with complex pathological process. Current chemotherapy faces problems such as lack of specificity, cytotoxicity, induction of multi-drug resistance and stem-like cells growth. Nanomaterials are materials in the nanorange 1–100 nm which possess unique optical, magnetic, and electrical properties. Nanomaterials used in cancer therapy can be classified into several main categories. Targeting cancer cells, tumor microenvironment, and immune system, these nanomaterials have been modified for a wide range of cancer therapies to overcome toxicity and lack of specificity, enhance drug capacity as well as bioavailability. Although the number of studies has been increasing, the number of approved nano-drugs has not increased much over the years. To better improve clinical translation, further research is needed for targeted drug delivery by nano-carriers to reduce toxicity, enhance permeability and retention effects, and minimize the shielding effect of protein corona. This review summarizes novel nanomaterials fabricated in research and clinical use, discusses current limitations and obstacles that hinder the translation from research to clinical use, and provides suggestions for more efficient adoption of nanomaterials in cancer therapy.
6. Antibody drug conjugate: the “biological missile” for targeted ...
Mar 22, 2022 · ... as auristatins and mytansinoids, with improved the water solubility and ... poor vascular innervation and central nervous system tumors.
Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as “biological missiles”, is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.
7. Natural Products as a Vital Source for the Discovery of Cancer ...
Dec 17, 2015 · Nevertheless, many suffer from the liabilities of poor solubility in aqueous media and significant toxic side effects. Thus, there continues ...
Abstract. Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy. Examples include Taxol, vinblastine, and camptothecin. These structurally unique agents function by novel mechanisms of action; isolation from natural sources is the only plausible method that could have led to their discovery. In addition to terrestrial plants as sources for starting materials, the marine environment (e.g., ecteinascidin 743, halichondrin B, and dolastatins), microbes (e.g., bleomycin, doxorubicin, and staurosporin), and slime molds (e.g., epothilone B) have yielded remarkable cancer chemotherapeutic agents. Irrespective of these advances, cancer remains a leading cause of death worldwide. Undoubtedly, the prevention of human cancer is highly preferable to treatment. Cancer chemoprevention, the use of vaccines or pharmaceutical agents to inhibit, retard, or reverse the process of carcinogenesis, is another important approach for easing this formidable public health burden. Similar to cancer chemotherapeutic agents, natural products play an important role in this field. There are many examples, including dietary phytochemicals such as sulforaphane and phenethyl isothiocyanate (cruciferous vegetables) and resveratrol (grapes and grape products). Overall, natural product research is a powerful approach for discovering biologically active compounds with unique structures and mechanisms of action. Given the unfathomable diversity of nature, it is reasonable to suggest that chemical leads can be generated that are capable of interacting with most or possibly all therapeutic targets.
8. Ch. 2: Chemical Components of Cells Flashcards Preview - Brainscape
You have developed a promising anti-cancer agent, but it has poor solubility in water. ... NOT ionic bonds – weak in aqueous solutions (water) NOT hydrogen bonds ...
Study Ch. 2: Chemical Components of Cells flashcards from Yeajin Park's class online, or in Brainscape's iPhone or Android app. ✓ Learn faster with spaced repetition.
