Folate decorated chitosan-chondroitin sulfate nanoparticles loaded hydrogel for targeting macrophages against rheumatoid arthritis.

Inflammatory cell infiltration, particularly macrophages, plays a major contribution to the pathogenesis of Rheumatoid Arthritis (RA). Exploiting the overexpression of folate receptors (FR-ß) on these recruited macrophages has gained significant attraction for ligand-targeted delivery. Leflunomide (LEF), being an immunomodulatory agent is considered the cornerstone of the therapy, however, its oral efficacy is impeded by low solubility and escalating adverse effects profile. Therefore, in the present work, we developed Folate-conjugated chitosan-chondroitin sulfate nanoparticles encapsulating LEF for selective targeting at inflammatory sites in RA. For this purpose, the folate group was first conjugated with the chitosan polymer. After which, Folate Leflunomide Nanoparticles (FA-LEF-NPs) were synthesized through the ionotropic gelation method by employing FA-CHI and CHS. The polymers CHI and CHS were also presented with innate anti-inflammatory and anti-rheumatic attributes that were helpful in provision of synergistic effects to the formulation. These nanoparticles were further fabricated into a hydrogel, employing almond oil (A.O) as a permeation enhancer. The in vivo studies justified the preferential accumulation of FA-conjugated nanoparticles at inflamed joints more than any other organ in comparison to the free LEF and LEF-NPs formulation. The FA-LEF-NPs loaded hydrogel also ascertained a minimal adverse effect profile with an improvement of inflammatory cytokines expression.

Polysaccharide Chemistry in Drug Delivery, Endocrinology, and Vaccines.

Polysaccharides, due to their outstanding properties, have attracted the attention of researchers, working in the biomedical field and especially of those working in drug delivery. Modified/functionalized polysaccharides further increase the importance for various applications. Delivery of therapeutics for diverse ailments in different endocrine glands and hormones safely, is a focal point of researchers working in the field. Among the routes followed, the transdermal route is preferred due to non-exposure of active moieties to the harsh gastric environment and first-pass metabolism. This review starts with the overview of polysaccharides used for the delivery of various therapeutic agents. Advantages of polysaccharides used in the transdermal route are addressed in detail. Types of polysaccharides will be elaborated through examples, and in this context, special emphasis will be on the polysaccharides being used for synthesis of the membranes/films. Techniques employed for their modification to design novel carriers for therapeutics delivery will also be discussed. The review will end with a brief discussion on recent developments and future perspectives for delivery of therapeutic agents, and vaccine development.

Co-encapsulating CoFe2O4 and MTX for hyperthermia.

Magnetic manotheranostics can be a fascinating charm to diagnose a tumour with MRI, and treatment through hyperthermia. This study aims to synthesise and characterise magnetically responsive polymer colloids (MRPCs). Healthy tissue damage done by chemotherapy session could be minimised by MRPCs. For the colloidal formulation of MRPCs, the oil in water emulsion technique was employed with the aid of sonication and stirring. The organic phase of emulsion contained methotrexate (MTX) drug, Eudragit E100 and CoFe2O4 (synthesised by co-precipitation) in ethanol, and the aqueous phase contained tween 80 in deionised water. The emulsion was optimised by studying/adjusting two different parameters, i.e. the concentration of constituents and sonication cycles. Multiple formulations were produced at sonication amplitude of 60% at 20 kHz, followed by centrifugation and lyophilisation. Characterisation of MRPCs was done for morphology, size measurement (23-25 nm), surface charge (∼15.12), coercivity (∼1549.6 G), magnetisation (2.6 emu) and retentivity (1.34 emu). Drug release in simulating physiological environment (pH = 7.4), was observed for up to 48 h, and, to determine the best release kinetic mechanism results were compared with kinetic models. Magnetic hyperthermia studies showed that MRPCs achieved an acceptable temperature of 42°C, for hyperthermia treatments in cancer patients.