Auto-fluorescent PAMAM-based dendritic molecules and their potential application in pharmaceutical sciences.

The epithelial permeation of water-soluble fluorescent PAMAM dendrons based on 7H-benz[de] benzimidazo [2,1-a] isoquinoline-7-one as a fluorescent core across epithelial cell models MDCK I and MDCK II has been quantified. Hydrodynamic radii have been derived from self-diffusion coefficients obtained via pulsed-gradient spin-echo Nuclear Magnetic Resonance (PGSE-NMR). Results indicate that these dendritic molecules are molecularly disperse, non-aggregating, and only slightly larger than their parent homologues. MDCK I permeability studies across epithelial barriers show that these dendritic molecules are biocompatible with the chosen epithelial in-vitro model and can permeate across MDCK cell monolayers. Permeability is demonstrated to be a property of dendritic size and cell barrier restrictiveness indicating that paracellular mechanisms play the predominant role in the transport of these molecules.

Humidified Warmed CO2 Treatment Therapy Strategies Can Save Lives With Mitigation and Suppression of SARS-CoV-2 Infection: An Evidence Review.

The coronavirus disease (COVID-19) outbreak has presented enormous challenges for healthcare, societal, and economic systems worldwide. There is an urgent global need for a universal vaccine to cover all SARS-CoV-2 mutant strains to stop the current COVID-19 pandemic and the threat of an inevitable second wave of coronavirus. Carbon dioxide is safe and superior antimicrobial, which suggests it should be effective against coronaviruses and mutants thereof. Depending on the therapeutic regime, CO2 could also ameliorate other COVID-19 symptoms as it has also been reported to have antioxidant, anti-inflammation, anti-cytokine effects, and to stimulate the human immune system. Moreover, CO2 has beneficial effects on respiratory physiology, cardiovascular health, and human nervous systems. This article reviews the rationale of early treatment by inhaling safe doses of warmed humidified CO2 gas, either alone or as a carrier gas to deliver other inhaled drugs may help save lives by suppressing SARS-CoV-2 infections and excessive inflammatory responses. We suggest testing this somewhat counter-intuitive, but low tech and safe intervention for its suitability as a preventive measure and treatment against COVID-19. Overall, development and evaluation of this therapy now may provide a safe and economical tool for use not only during the current pandemic but also for any future outbreaks of respiratory diseases and related conditions.

Influence of photoinitiator concentration and irradiation time on the crosslinking performance of visible-light activated pullulan-HEMA hydrogels.

In-situ forming hydrogels were prepared from pullulan-HEMA copolymer using three-component visible-light system composed of camphorquinone carboxylic acid-folic acid-iodonium salt. The relevance of double bond conversion and crosslinking density of hydrogels with the photoinitiator concentration and irradiation time were estimated by FT-IR analysis and swelling calculation using Flory-Rehner theory, respectively. The results revealed that the crosslinking density and degree of conversion of hydrogels were improved by photoinitiator concentration increasing until certain extend, then they decreased due to a primary radicals termination reaction occurred. The shortest irradiation time of 10 s was essential to obtain acceptable hydrogels for further characterizations. For the probability use of hydrogels as scaffold was investigated in vitro by measuring of the indirect cytotoxicity assay by MTT-assay using human bone Sarcoma cell as a reference cell lines. The majority of seeded SW1353 cells maintained a live with an accepted viability of ~85-92% over a four days culture period with irradiation of hydrogel 10 s, while cell viability has improved to ~95-98% with prolonging the irradiation time of hydrogel to 60 s. The current photoinitiating system is a proper system for in-situ crosslinking the activated-light biomaterials for bone regeneration, dental, or tissue engineering applications.

Thermoresponsive and Reducible Hyperbranched Polymers Synthesized by RAFT Polymerisation.

Here, we report the synthesis of new thermoresponsive hyperbranched polymers (HBPs) via one-pot reversible addition-fragmentation chain transfer (RAFT) copolymerisation of poly(ethylene glycol)methyl ether methacrylate (PEGMEMA, Mn = 475 g/mol), poly(propylene glycol)methacrylate (PPGMA, Mn = 375 g/mol), and disulfide diacrylate (DSDA) using 2-cyanoprop-2-yl dithiobenzoate as a RAFT agent. DSDA was used as the branching agent and to afford the HBPs with reducible disulfide groups. The resulting HBPs were characterised by Nuclear Magnetic Resonance Spectroscopy (NMR) and Gel Permeation Chromatography (GPC). Differential Scanning Calorimetry (DSC) was used to determine lower critical solution temperatures (LCSTs) of these copolymers, which are in the range of 17⁻57 °C. Moreover, the studies on the reducibility of HBPs and swelling behaviours of hydrogels synthesized from these HBPs were conducted. The results demonstrated that we have successfully synthesized hyperbranched polymers with desired dual responsive (thermal and reducible) and crosslinkable (via thiol-ene click chemistry) properties. In addition, these new HBPs carry the multiplicity of reactive functionalities, such as RAFT agent moieties and multivinyl functional groups, which can afford them with the capacity for further bioconjugation and structure modifications.