We show the synthesis method of red emissive gold nanocluster conjugated crumpled MXene nanosheets. This material was applied as bio-imaging and PTT agent. The in vivo toxicity was performed in rats via both the oral and I.V. modes of administration.

Currently, intelligent, responsive biomaterials have been widely explored, considering the fact that responsive biomaterials provide controlled and predictable results in various biomedical systems. Responsive nanostructures undergo reversible or irreversible changes in the presence of a stimulus, and that stimuli can be temperature, a magnetic field, ultrasound, pH, humidity, pressure, light, electric field, etc. Different types of stimuli being used in drug delivery shall be explained here. Recent research progress in the design, development and applications of biomaterials comprising responsive nanostructures is also described here. More emphasis will be given on the various nanostructures explored for the smart stimuli responsive drug delivery at the target site such as wound healing, cancer therapy, inflammation, and pain management in order to achieve the improved efficacy and sustainability with the lowest side effects. However, it is still a big challenge to develop well-defined responsive nanostructures with ordered output; thus, challenges faced during the design and development of these nanostructures shall also be included in this article. Clinical perspectives and applicability of the responsive nanostructures in the targeted drug delivery shall be discussed here.

Introduction Ursolic acid (UA) and oleanolic acid (OA) are triterpenoids. They are used to treat numerous diseases, including tuberculosis. Combinations of these drugs provide new insight into the management of tuberculosis. The major obstacle is the effective delivery of these drugs to the lungs, which are mainly affected due to M. tuberculosis. A metered-dose inhaler (MDI) was developed to address this issue containing UA and OA, followed by in-vitro and in-vivo evaluation. Methods In the present study, MDI formulation was prepared by incorporating UA and OA at the dose level of 120 μg/ml in each actuation. In-vitro evaluation of this MDI formulation was performed to ensure its suitability to deliver UA and OA preciously. With prior approval of IAEC, a pharmacokinetic and acute inhalation toxicity study was conducted using MDI on Wistar rats. Results The pharmacokinetic study showed an increased biological half-life of UA (9.23±0.104 h) and OA (8.93±0.166 h) in combination therapy. In-vivo toxicity study demonstrated no adverse effects on body weight and vital organs in the treatment group compared with the control group. Histopathology examination of these essential organs showed no abnormalities. Mild alternation in the biochemical and hematological parameters was observed. However, these alterations did not affect the overall health of the animals. Conclusion The present study documents a detailed study for the safety and pharmacokinetics of UA and OA in-vivo for their advanced application in tuberculosis disease.

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