Chitosan, the deacetylated form of chitin, a natural polysaccharide, is known for its various biomedical applications. The present study aimed at exploring the immunomodulatory properties of chitosan (CSNP) and gallic acid‐grafted chitosan (cGANP) nanoparticles in mice model of cyclophosphamide (CPA)‐induced immunosuppression. In addition, chitooligosaccharides, the hydrolysed form of chitin and chitosan, were also evaluated for its potential against immunosuppression in mice. CPA (80 mg/kg/ip) induced significant immunosuppression, which was reversed with cGANP treatment as indicated by a significant increase in the thymus and spleen indices compared to the CPA‐treated group. The CSNP and chitooligosaccharides (chitin and chitosan) failed to reverse CPA‐induced changes. ELISA revealed an elevation in the levels of IL‐6 and a reduction in IFN‐γ levels with CPA treatment. All the test compounds reduced the IL‐6 levels, whereas only the nanoparticle formulations (CSNP and cGANP) exhibited a significant augmentation in the IFN‐γ levels. Both the cytokines, IL‐6 and IFN‐γ, are secreted separately by two different types of T helper cells (Th cells), which mediate cellular and humoral immune responses in a coordinated manner. Th‐1 cells release IFN‐γ, facilitating cell‐mediated immunity, whereas IL‐6 is released by Th‐2 cells, expediting humoral immune response. The nanoparticles (CSNP and cGANP) seemed to be better immune enhancers than the chitooligosaccharides owing to their ability to reverse the cytokine changes induced by CPA. Overall, it was evident that the nanoparticles, most likely, boosted the cell‐mediated immunity through the induction of the Th‐1 branch of the immune response. 相似文献
Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.
Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.
Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS. 相似文献