Current Pharmaceutical Design - Volume 28, Issue 39, 2022

Diabetes has become a serious threat to human health, causing death and pain to numerous patients. Transdermal insulin delivery is a substitute for traditional insulin injection to avoid pain from the injection. Transdermal methods include non-invasive and invasive methods. As the non-invasive methods could hardly get through the stratum corneum, minimally invasive devices, especially microneedles, could enhance the transappendageal route in transcutaneous insulin delivery, and could act as connectors between the tissue and outer environment or devices. Microneedle patches have been in quick development in recent years and with different types, materials and functions. In those patches, the smart microneedle patch could perform as a sensor and reactor responding to glucose to regulate the blood level. In the smart microneedles field, the phenylboronic acid system and the glucose oxidase system have been successfully applied on the microneedle platform. Insulin transdermal delivery strategy, microneedles technology and smart microneedles’ development would be discussed in this review.

The current coronavirus disease (COVID-19) pandemic has affected millions of individuals worldwide. Despite extensive research efforts, few therapeutic options currently offer direct clinical benefits for COVID-19 patients. Despite the advances in our understanding of COVID-19, the mortality rates remain significantly high owing to the high viral transmission rates in several countries and the rise of various mutations in the SARS-CoV-2. One currently available and widely used drug that combines both anti-inflammatory and immunomodulatory actions is colchicine, which has been proposed as a possible treatment option for COVID-19. Colchicine still did not get much attention from the medical and scientific communities despite its antiinflammatory and immunomodulatory mechanisms of action and positive preliminary data from early trials. This literature review article provides the scientific rationale for repurposing colchicine as a potential therapy for COVID-19. Further, we summarize colchicine’s mechanisms of action and possible roles in COVID-19 patients. Finally, we supplement this review with a summary of the doses, side effects, and early efficacy data from clinical trials to date. Despite the promising early findings from multiple observational and clinical trials about the potential of colchicine in COVID-19, the data from the RECOVERY trial, the largest COVID-19 randomized controlled trial (RCT) in the world, showed no evidence of clinical benefits in mortality, hospital stays, or disease progression (n = 11340 patients). However, multiple other smaller clinical trials showed significant clinical benefits. We conclude that while current evidence does not support the use of colchicine for treating COVID-19, the present body of evidence is heterogeneous and inconclusive. The drug cannot be used in clinical practice or abandoned from clinical research without additional large RCTs providing more robust evidence. At present, the drug should not be used except for investigational purposes.

Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer.

Background: Intravenous route of drug administration has maximum bioavailability, which shows 100% of the drug reaches blood circulation, whereas the oral administration of drugs, are readily undergoing pre-systemic metabolism, which means the poor bioavailability of the drug and limited amount of drug reaches the target site. Introduction: Bioenhancers are substances having medicinal entities which enhance the bioavailability and efficacy of the active constituents of drugs. The enhanced bioavailability of drugs may lead to dose reduction, which may further reduce the cost and undesired side effects associated with the drugs. Methods: The solid lipid nanoparticles (SLNs) loaded with ketoprofen made from carnauba wax and beeswax. It was discovered that when the drug-loaded SLNs were mixed with egg-lecithin and Tween-80, as well as when the total surfactant concentration was increased, the average particle size of the drug-loaded SLNs decreased. Results: The drug-loaded nanoparticles, when given in combination with bio-enhancers such as piperine and quercetin, enhanced the drug's effectiveness. The Area Under Curve (AUC) was increased when the drug was coupled with bio-enhancers. Based on the findings, it can be concluded that piperine and quercetin when used with drug-loaded nanoparticles improve their therapeutic effectiveness. Conclusion: Bioenhancers are crucial to amplifying the bioavailability of many synthetic drugs. These attributes are useful to reduce the dose of drugs and increase the therapeutic efficacy of drugs with poor bioavailability.

Background: Coronavirus Disease-19 (COVID-19) is implicated in endotheliitis, which adversely affects cardiovascular events. The impact of vaccination with COVID-19 on the clinical outcome of patients is documented. Objective: To evaluate the impact of vaccination with COVID-19 on the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection-related endothelial impairment. Methods: We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical and laboratory data were collected, and brachial artery flow-mediated dilation (FMD) was evaluated. Subjects without COVID-19 were used as the control group. Results: There was no difference in age (64.7 ± 7.5 years vs. 61.2 ± 11.1 years vs. 62.4 ± 9.5, p = 0.28), male sex (49% vs. 60% vs. 52%, p = 0.71), control subjects, vaccinated, and unvaccinated subjects with COVID-19, respectively. Of the patients with COVID-19, 44% were vaccinated against SARS-CoV-2. Unvaccinated COVID-19 patients had significantly impaired FMD compared to vaccinated COVID-19 patients and Control subjects (2.05 ± 2.41 % vs. 7.24 ± 2.52% vs. 7.36 ± 2.94 %, p <0.001). Importantly, post hoc tests revealed that unvaccinated COVID-19 patients had significantly impaired FMD from both Vaccinated COVID-19 subjects (p <0.001) and from Control subjects (p <0.001). There was no difference in FMD between the control group and the vaccinated COVID-19 group (p = 0.99). Conclusion: Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well compared to vaccinated patients with COVID-19. Vaccinated hospitalized subjects with COVID-19 do not show endothelial dysfunction, strengthening the protective role of vaccination against SARS-CoV-2.

Background: In recent years, the prevalence and mortality of autism spectrum disorder (ASD) have been increasing. The clinical features are different with different cases, so the treatment ways are different for each one. Objective: Baohewan Heshiwei Wen Dan Tang (BHWDT) has been recommended for treating autistic spectrum disorder. To investigate the mechanism of action and how the compounds interact with ASD targets, network pharmacology and molecular docking methods were used in this study. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the active components according to index of oral bio-activity and drug-likeness. Then, TCMSP and Swiss Target Prediction databases were used to screen potential target genes of active components. The related target genes of ASD were obtained from the Gene Cards database. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. Composition- target-pathway (C-T-P) and a protein-protein interaction (PPI) networks were built with Cytoscape 3.8.2 software. Results: The interaction of the main active components of BHWDT was verified by molecular docking. The key targets of MAPK1, IL6, CXCL8 and TP53 of BHWDT were obtained. The key active components Quercetin, Kaempferol and Iuteolin of BHWDT could bind with MAPK1, IL6, CXCL8 and TP53 of BHWDT, respectively. Conclusion: BHWDT can be highly effective for treating ASD and this study can help us to understand multiple targets and multiple pathways mechanism.