Preparation and Characterization of Disulfiram and Beta Cyclodextrin Inclusion Complexes for Potential Application in the Treatment of SARS-CoV-2 via Nebulization

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl β-cyclodextrin (HP) and sulfobutyl ether β-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS–CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD–DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS–CD inclusion complexes against SARS-CoV-2 via nebulization

Preliminary SAR on indole-3-carbinol and related fragments reveals a novel anticancer lead compound against resistant glioblastoma cells

The prognosis for glioblastoma patients is, at best, poor, with the median time of survival after diagnosis measured in months. As such, there is much need for the rapid development of potent and novel treatments. Herein, we report our preliminary findings on the SAR of a series of indole-3-carbinol and related fragments and reveal a potent lead with low micromolar activity against a particularly resistant glioblastoma cell culture, providing a new platform for future development of a new therapy in this area

Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines

Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells

Cyclodextrin diethyldithiocarbamate copper ii inclusion complexes: A promising chemotherapeutic delivery system against chemoresistant triple negative breast cancer cell lines

Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells.Funding: This research is funded by NPRP grant (NPRP9-337-3-069) from the Qatar National Funding: This research is funded by NPRP grant (NPRP9-337-3-069) from the Qatar National Re-Research Fund (a member of Qatar Foundation). The findings herein reflect the work, and are solely search Fund (a member of Qatar Foundation). The findings herein reflect the work, and are solely the responsibility, of the authors. the responsibility, of the authors.Scopu

Development, characterization and stability evaluation of ciprofloxacin-loaded parenteral nutrition nanoemulsions

In this study, two licensed total parenteral nanoemulsion formulations (Clinoleic® and Intralipid®) were loaded with ciprofloxacin (CP). The physicochemical characteristics and stability profiles of the formulations were investigated using a range of drug concentrations. Furthermore, formulation stability was evaluated over a period of six months at room temperature or 4 °C. Loading CP into nanoemulsions resulted in no significant differences in their measured droplet size, polydispersity index (PI), zeta potential and pH. Drug entrapment efficiency (EE) was relatively high for all formulations, regardless of nanoemulsion type, and the drug release was sustained over 24 h. Stability studies of all formulations were performed at 4 °C and room temperature (RT) for 180 and 60 days, respectively. At 4 °C for 180 days, both Clinoleic and Intralipid formulations at a range of drug concentrations (1-10 mg/ml) showed high stabilities measured periodically by the average droplet sizes, PI, pH and zeta potential values. Similar results, but pH values, were shown when the formulations for both nanoemulsion stored at RT for 60 days. Overall, this study has shown that CP was successfully loaded into clinically licensed TPN lipid nanoemulsions. The resultant CP-loaded nanoemulsion formulations demonstrated desirable physicochemical properties and were stable upon storage at 4 °C for up to six months

Preparation and characterisation of zinc diethyldithiocarbamate–cyclodextrin inclusion complexes for potential lung cancer treatment

Zinc diethyldithiocarbamate (Zn (DDC)2), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC)2 is investigated by forming inclusion complexes with cyclodextrins. The inclusion complexes were prepared using two different types of beta-cyclodextrins, SBE-CD and HP-CD. Phase solubility diagrams for the resulting solutions were assessed; subsequently, the solutions were freeze-dried for further characterisation studies using DSC, TGA, XRD, and FTIR. The cytotoxic activity of the produced inclusion complexes was evaluated on human lung carcinoma cells using the MTT assay. The solubility of Zn (DDC)2 increased significantly upon adding beta-cyclodextrins, reaching approximately 4 mg/mL for 20% w/w CD solutions. The phase solubility diagram of Zn (DDC)2 was of the Ap-type according to the Higuchi and Connors model. Characterisation studies confirmed the inclusion of the amorphous drug in the CD-Zn (DDC)2 complexes. The cytotoxicity of Zn (DDC)2 was enhanced 10-fold by the inclusion complexes compared to the free drug. Overall, the resulting CD-Zn (DDC)2 inclusion complexes have a potential for treatment against lung cancer

The Association of Academic Cosmetic Dermatology: improving cosmetic dermatology education through collaboration, research, and advocacy.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy

Needs and Gaps in Resident Trainee Education, Clinical Patient Care, and Clinical Research in Cosmetic Dermatology: Position Statement of the Association of Academic Cosmetic Dermatology.

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward