Development of biomedical hydrogels for rheumatoid arthritis treatment

Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and women.Therefore,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating RA.This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale.Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic applications.Hydrogels are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid.Hence,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction.Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating RA.This work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and challenges.Additionally,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.

A DNA-based nanocarrier for efficient cancer therapy

The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread(CPT-DNA-NT),mediated by scavenger receptors into HeLa cells.DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT.Atomic force microscopy(AFM)characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm.The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis,as large the molecular-weight(polymeric)DNA-NT did not split into constituting strands under applied current and voltage.The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration(512 nM)with a viability of 92%as evidence of its biocompatibility for drug delivery.MTT assay showed superior cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization.The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT(from DNA-NT),as illustrated in confocal images.Therefore,in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis(72.7%)with CPT-DNA-NT(compared to free CPT;64.4%).CPT-DNA-NT,being poly-anionic,showed enhanced endocytosis via scavenger receptors.

Tylophora hirsuta L. leaf extract attenuates alloxan-induced diabetes in mice by suppressing oxidative stress and α-amylase

Objective:To evaluate the antidiabetic potential of leaf extracts of Tylophora hirsuta(T.hirsuta).Methods:The methanolic and ethyl acetate extracts of T.hirsuta leaves were analyzed by high pressure liquid chromatography.In vitro antioxidant activity was determined by ferric ion reduction,1,1-diphenyl-2-picrylhydrazyl,and hydrogen peroxide scavenging methods.In vitro alpha amylase(α-amylase)inhibitory activity of the plant extracts was assessed.In vivo antidiabetic potential was determined in alloxan-induced diabetic mice to assess glycated hemoglobin(HbA1c),oral glucose tolerance,serum amylase,lipid profile,fasting blood glucose,and body weight.Histopathological lesions of the pancreas,liver and kidney were observed.Oxidative stress biomarkers such as superoxide dismutase,catalase and peroxidase were also determined.Results:Quercetin,chlorogenic acid,p-coumaric acid,and m-coumaric acid were found in the plant extracts.The methanolic plant extract exhibited higher in vitro antioxidant activities than the ethyl acetate extract.Moreover,methanolic plant extract exhibited(83.90±1.56)%α-amylase inhibitory activity at 3.2 mg/mL concentration.Animal study showed that the methanolic extract of T.hirsuta improved the levels of fasting blood glucose,HbA1c,serumα-amylase,lipid profile,liver function biomarkers,and kidney functions of diabetic mice.Moreover,the methanolic extract ameliorated diabetes-related oxidative stress by increasing superoxide dismutase and catalase activities and decreasing peroxidase and malondialdehyde levels.Histopathological examination showed that the plant extract had improved the integrity of pancreatic islets of Langerhans and reduced the pathological lesions in the liver and kidney of diabetic mice.Conclusions:The methanolic extract of T.hirsuta exhibits pronounced antidiabetic activity in mice through reduction of oxidative stress.The plant extract has several natural antioxidants such as phenolic acids.T.hirsuta extract could serve as a nutraceutical for managing diabetes mellitus.

The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors

DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand(84-NT) was the critical step followed by annealing with various staple strands to make stiff DNAtriangles. Atomic force microcopy(AFM), native polyacrylamide gel electrophoresis(PAGE), UVanalysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 mm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane(500 bp level) with the loss of electrophoretic mobility during the PAGE(native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNANWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22%) compared to the apoptosis(7%)induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC_(50) of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC_(50) of 51.2 n M.Confocal imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2) compared with the control cell line.

Corrigendum to“The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors”[Journal of Pharmaceutical Analysis volume 11(2021)174e182]

The authors regret to inform that Figs.4,6,and 7 in the original article were wrongly selected.The corrected figures appear below:The authors would like to apologize for any inconvenience caused.

DNA Nanotechnology for Modulating the Growth and Development of Neurons

Late prenatal growth,early postnatal growth,and layering of the neocortical neurons(NC-Ns)play determining roles in the development of the cerebral cortex(CC).Here,we systematically explore the interactive role of neuronal surface receptors(NSRs)on cytoskeleton activation(CA)and the piconewton(pN)force generation(P-FG)and their influence on the proper development,growth,and functioning of neurons using a designed DNA nanomechanical device(DNA-NMD).