Dual Thermo- and Photo-Responsive Micelles Based on Azobenzene-Containing Random Copolymer

Amphiphilic random copolymer poly(methacrylamido-azobenzene)-ran-poly(2-hydroxyethylacrylate) (PMAAAB-ran-PHEA) was synthesized via hydrolysis of poly(methacrylamido-azobenzene)-ran-poly[2-((2′-tetrahydropyranyl)oxy)ethylacrylate] (PMAAAB-ran-P(THP-HEA)), which was prepared by conventional radical polymerization. PMAAAB-ran-PHEA micelles were then prepared via dialysis method against water with DMF as solvent. The structure, morphology, size, and low critical solution temperature (LCST) of PMAAAB-ran-PHEA and its micelles were determined by 1H-NMR, GPC, TEM, and DLS. The thermo- and photo-responsive behaviors of the resulting polymer micelles were investigated with Nile red as a fluorescence probe. The results showed that PMAAAB-ran-PHEA micelles were porous or bowl-shaped and its size was 135–150 nm, and its LCST was 55 °C when FMAAAB of the random copolymer was 0.5351; the hydrophobicity of the micellar core was changed reversibly under the irradiation of UV light and visible light without release of Nile red or disruption of micelles; the size and solubilization capacity of the micelles were dependent on temperature, and Nile red would migrate for many times between the water phase and the micelles, and finally increasingly accumulated during the repeated heating and cooling processes.

A novel method for producing functionalized vesicles that efficiently deliver oligonucleotides in vitro and in vivo in mice

Nano-based delivery systems have greatly enhanced our ability to administer and target drugs and macromolecules to their therapeutic targets. Oligonucleotide drugs have great therapeutic potential but have off-target effects and stability issues, so they are often encapsulated in functionalized vesicles with targeting ligands such as antibodies (Ab). Herein, we describe a novel, scalable and straightforward approach to produce functionalized vesicles called the “Functionalized Lipid Insertion Method.” This method differs significantly from an older approach referred to as the “Detergent-Dialysis Method.” The older method requires excess detergent and extensive dialysis over many hours to produce the functionalized vesicles. With the “Functionalized Lipid Insertion Method,” only the functionalized lipid is detergent-solubilized during the formation of the functionalized vesicle. The approach reduces the dialysis time, keeps the vesicle intact, and orients the functionalized lipid to improve targeting compared to the older method. The dynamic light scattering (DLS) technique demonstrated that vesicle size is sensitive to the initial detergent-solubilized component mixture by the older method. In contrast, functionalized vesicle size increases are consistent with functionalized lipid insertion into the vesicle. In vitro, functionalized vesicles using our approach are able to deliver oligonucleotides selectively and can functionally affect liver cancer HepG2 cells. Functionalized vesicles produced by this method can also achieve targeted delivery of oligonucleotides in mice without inducing a significant immune response through cytokine production or showing physical signs of an immune response. The industrial and therapeutic significance and implications of functionalized vesicles produced by our method are also discussed.

Design, Formulation, and Physicochemical Evaluation of Occimum sanctum Containing Honey Based Hydrogel

Background and Aim: The present study aims to formulate a hydrogel containing Tulsi (O. sanctum) and honey, to obtain a pharmaceutical topical preparation having desirable healing effects and antibacterial properties of both the ingredients. Material and Method: Topical honey hydrogel formulation were prepared using 75%honey and 10% Occimum sanctum (Tulsi) with polymer carbopol 934. The prepared formulation was assessed for its pH, spreadability, swelling index and in-vitro release Result: The pH and spreadability were in the range of 4.74 ± 0.02 and 7.75 ± 0.04 cm respectively. Carbopol based Honey –Tulsi Formulation showed a concentration-dependent increase in the amount of honey and O. sanctum diffused through dialysis method. Conclusion: Within the limitations of the study, the results of our present study suggest that the studied Honey –Tulsi based hydrogel could be an economic indigenous substitute which is non-toxic, natural and efficient for clinical application.

The analysis of the permeability process of calcium antagonists in developing transdermal forms with a cardiovascular effect

Aim. The aim of the work was to evaluate the possibility of using calcium antagonists, namely, nifedipine and amlodipine besylate, while conducting transdermal delivery, that included the analysis of in vitro permeability process as a primary preformulation stage of pharmaceutical development of a transdermal dosage form, determination of qualitative and quantitative characteristics of a permeability process and the expediency analysis of development of a therapeutic transdermal system (TTS) with a cardiovascular effect. Materials and methods. The active pharmaceutical ingredients (API) of nifedipine and amlodipine besylate. The study has been carried out in vitro by a dialysis method using a modified diffusion device of the Valia-Chien design. Results. Character analysis, description of the mathematical model and definition of the kinetic parameters in the process of permeability of the studied medicinal products (MP) of nifedipine and amlodipine besylate allowed to evaluate their potential for creating TTS as being positive and appropriate. The implemented methodological approaches allow to substantiate the further algorithm for the development of cardiovascular TTS with the mentioned API.

Designing a National Haemodialysis Registry Model for Iran

Introduction: The global prevalence of End-Stage Renal Disease (ESRD) requiring therapeutic dialysis is on the rise. Haemodialysis is the main therapeutic dialysis method. Evaluating its effectiveness and planning to promote the quality of care and epidemiological research necessitate the development of registries as the main management tool. Aim: To design a national haemodialysis registry model for Iran. Materials and Methods: This was an applied descriptive study. Based on a review of articles and information sources, and a comparative study of national hemodialysis registries in developed countries, a national haemodialysis registry model was designed for Iran. After confirming the reliability and validity of the questionnaire, the designed model was given to nephrologists in a two-stage Delphi technique, and their comments were applied to the final model. Results: The presented national haemodialysis registry model main components consist of: goals, structure, data sources, minimum dataset, standards, and processes, all of which received 100% expert consensus. Conclusion: This registry is a powerful database for the progress of treatment, understanding changes in the treatment and outcomes, examining the factors affecting prognosis and quality of life.

Study on the Plasma Protein Binding Rate and Compatibility Regularity of the Constituents Migrating to Blood of Simiao Yong’an Decoction

Objective: To study the compatibility regularity of Simiao Yong’an decoction by determining the plasma protein binding rate with the constituents in Simiao Yong’an decoction and to preliminarily clarify the effects of the compatibility on the plasma protein binding rate of different components. Methods: Based on the equilibrium dialysis method, high-performance liquid chromatography was used to determine the contents of six constituents, which were divided into a single group and combination groups, in Simiao Yong’an decoction in the internal and external dialysis solutions. The obtained plasma protein binding rate through calculations was an index to evaluate the binding of the above components to plasma protein in different conditions. Results: Harpagide, harpagoside, sweroside and loganin showed low plasma protein binding rates, ferulic acid exhibited a moderate plasma protein binding rate, and glycyrrhizic acid showed a high plasma protein binding rate. The compatibility study showed that glycyrrhizic acid promoted the binding of ferulic acid to plasma protein. Glycyrrhizic acid and ferulic acid were the key compounds to promote the binding of harpagide to plasma protein. Glycyrrhizic acid, harpagide, harpagoside and loganin had a significant inhibitory effects on the binding of sweroside to plasma protein. The plasma protein binding capacities of harpagoside and loganin were reduced by the other five constituents. Glycyrrhizic acid had the strongest plasma protein binding effect, and the binding effect was not affected by other components. Conclusions: This study explores the effects of compound compatibility on effective components from the perspective of plasma protein binding by high-performance liquid chromatography combined with the equilibrium dialysis method, and lays a foundation for clarifying the compatibility rule of Simiao Yong’an decoction and also provides a new idea for the study of the compatibility of traditional Chinese medicine formulas.

A Review on Polymeric Nano Micelles Based Delivery to the Posterior Segment of the Eye

Introduction: Many nanoformulations have been designed and evaluated for ocular drug delivery system consistently. These nanoformulations are designed for prolonged retention and course time, stable, efficient and reversible drug loading. The ocular bioavailability is very less when the drug is given through topically. Various anatomical and physiological limitations, for example, tear turnover, nasal lachrymal waste, reflex squinting, and visual static and dynamic hindrances cause the challenges and delay the ocular drug permeation because of the limitation that less than 5% dose can reach into the ocular tissues. Different types of Polymeric micelles were prepared to overcome the above challenges. Polymeric nano micelles are prepared by different methods, such as direct dissolution, dialysis method, Oil-in-water emulsion, solvent evaporation, co-solvent evaporation, and freeze-drying method.

Which dialysis method should be used for patients with COVID-19?

KEY FINDINGS• Very low-quality evidence from a single retrospective study suggests that continuous renal replacementtherapy (CRRT) may reduce mortality among COVID-19 patients on invasive mechanical ventilation. Guidelinesrecommend CRRT for critically ill patients to minimize the risk of possible transmission, if this option is available.• Although uncommon, acute kidney injury (AKI) can occur in association with coronavirus disease 2019(COVID-19) and is associated with increased in-hospital mortality.• There are currently no published or ongoing clinical trials directly comparing dialysis modalities for acutekidney injury in COVID-19 patients.• In reducing the risk of transmission during dialysis: currently, there are no studies comparing one dialysismodality to another. The method of dialysis is still primarily determined by the clinical picture of the patient, theexpertise of the center, and the resources available. The American Society of Nephrology (ASN) recommendsCRRT over intermittent hemodialysis (IHD) for critically ill patients with COVID-19 to minimize patient contactwhen it is available, and resources allow. Otherwise, intermittent hemodialysis may be done provided that,infection control measures are strictly followed.• Several international and local guidelines recommend strict adherence to infection prevention and controlmeasures (e.g. hand hygiene, physical distancing, proper use of personal protective equipment (PPE), andcohorting of patients) who are undergoing dialysis.

Fabrication and Characterization of Ceftizoxime-Loaded Pectin Nanocarriers

Ceftizoxime (C13H12N5NaO5S2) is a parenteral, third-generationcephalosporin antibiotic used to treat bacterial infections including ear, nose, and throat infections. In this work, pectin has been used as a nanocarrier for ceftizoxime due to its high biocompatibility and non-toxicity with tunable surface properties. Ceftizoxime-loaded pectin nanocarriers (CPN) were successfully synthesized by the solvent displacement method. Optimization of nanoformulation was done by response surface methodology using Design-Expert software. The optimized formulation examined various in-vitro characterizations such as particle size, morphology, and FTIR studies. TEM results revealed irregular shape nanoparticles within the range of 29–110 nm. The in-vitro drug release using the dialysis method was performed after 24 h where nanoformulation showed sustained drug release. Drug-loaded nanoparticles revealed good antimicrobial activity against Bacillus cereus, Bacillus polymyxa, Enterobacter aerogenes, and Pseudomonas aeruginosa.