Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review.

Purpose: To develop polymeric nanosponge based hydrogel system of fluconazole (FZ) for improved delivery for topical application. Method: Six different nanosponge preparations of fluconazole were formulated by oil-in-water (o/w) emulsion solvent diffusion method using various drug to polymer (ethylcellulose, EC) ratios. Polyvinyl alcohol (PVA) and dichloromethane were used to prepare the aqueous and dispersed phases, respectively. The nanosponges (NS) were studied for entrapment efficiency, particle size, structural properties, size and appearance, and in vitro drug release. Furthermore, the hydrogel formulation was evaluated for ex vivo permeation characteristics. Results: Morphological studies revealed porous nanosized particles with the outer surface resembling orange peel. The nanosponges had particle size in the range of 220.2 ± 4.5 to 624.1 ± 10.4 nm. Release studies showed 43.9 ± 3.2 % drug release at 6 h, confirming the sustained release pattern of the drug-loaded nanosponges. Powder x-ray diffraction (PXRD) and Fourier transform infra-red (FTIR) analyses indicate complex formation in the nanosponge structure. Out of six nanosponge formulations prepared, F3 containing FZ and EC in the ratio of 1:0.7 showed optimum physicochemical and release characteristics and, therefore, was selected for hydrogel formulation. Kinetic analysis of the permeation data revealed a Higuchi diffusion pattern. Ex vivo permeation studies indicate that the hydrogel preparation displayed adequate drug permeation through rat abdominal skin. Conclusion: A nanosponge-loaded hydrogel of fluconazole for improved permeation of the drug through skin has been successfully developed. Safety and toxicity tests are required to ascertain its potential suitability for use in humans.

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