Recent efforts in designing nanomaterials to deliver potential therapeutics to the targeted site are overwhelming and palpable. Engineering nanomaterials to deliver biological molecules to exert desirable physiological changes, with minimized side effects and optimal dose, has revolutionized the next-generation therapy for several diseases. The rapid progress of nucleic acids as biopharmaceutics is going to alter the traditional pharmaceutics practices in modern medicine. However, enzymatic instability, large size, dense negative charge (hydrophilic for cell uptake), and unintentional adverse biological responses—such as prolongation of the blood coagulation and immune system activation—hamper the potential use of nucleic acids for therapeutic purposes. Moreover, the safe delivery of nucleic acids into the clinical setting is an uphill task, and several efforts are being put forward to deliver them to targeted cells. Advances in Metal-based NanoParticles (MNPs) are drawing attention due to the unique properties offered by them for drug delivery, such as large surface-area-to-volume ratio for surface modification, increased therapeutic index of drugs through site-specific delivery, increased stability, enhanced half-life of the drug in circulation, and efficient biodistribution to the desired targeted site. Here, the potential of nanoparticles delivery systems for the delivery of nucleic acids, specially MNPs, and their ability and advantages over other nano delivery systems are reviewed. Graphical Abstract

Skeletal disabilities are a prominent burden on the present population with an increasing life span. Advances in osteopathy have provided various medical support for bone-related diseases, including pharmacological and prosthesis interventions. However, therapeutics and post-surgery complications are often reported due to side effects associated with modern-day therapies. Thus, therapies utilizing natural means with fewer toxic or other side effects are the key to acceptable interventions. Flavonoids constitute a class of bioactive compounds found in dietary supplements, and their pharmacological attributes have been well appreciated. Recently, flavonoids’ role is gaining renowned interest for its effect on bone remodeling. A wide range of flavonoids has been found to play a pivotal role in the major bone signaling pathways, such as wingless-related integration site (Wnt)/β-catenin, bone morphogenetic protein (BMP)/transforming growth factor (TGF)-β, mitogen-activated protein kinase (MAPK), etc. However, the reduced bioavailability and the absorption of flavonoids are the major limitations inhibiting their use against bone-related complications. Recent utilization of nanotechnological approaches and other delivery methods (biomaterial scaffolds, micelles) to target and control release can enhance the absorption and bioavailability of flavonoids. Thus, we have tried to recapitulate the understanding of the role of flavonoids in regulating signaling mechanisms affecting bone remodeling and various delivery methods utilized to enhance their therapeutical potential in treating bone loss.

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