A triple combination 'nano' dry powder inhaler for tuberculosis: in vitro and in vivo pulmonary characterization.

Inhalation route of drug delivery is the most favorable for pulmonary infections wherein direct drug delivery is desired to the lungs. Tuberculosis is one such infection suffering from poor therapeutic efficacy because of low patient compliance due to high drug dosing and lengthy treatment protocols. The current research work was undertaken to develop a dry powder inhaler (DPI) for administration of three first-line antitubercular antibiotics directly to the lungs to improve the treatment rates. Nanoformulations of isoniazid, pyrazinamide, and rifampicin were prepared, spray-dried to obtain a dry powder system, and blended with inhalation grade lactose to develop the DPI. The DPI was evaluated for its flow properties, pulmonary deposition, dissolution profile, and stability. The DPI possessed excellent flow properties with a fine particle fraction of 45% and a mass median aerodynamic diameter of approximately 5 µm indicating satisfactory lung deposition. In vitro drug release exhibited a sustained release of the formulations. In vivo studies showed a prolonged deposition in the lung at elevated concentrations compared to oral therapy. Stability studies proved that the formulation remained stable at accelerated and long-term stability conditions. The DPI could complement the existing oral therapy in enhancing the therapeutic efficacy in patients.

Detoxification of Abrus precatorius L. seeds by Ayurvedic Shodhana process and anti-inflammatory potential of the detoxified extract.

BACKGROUND: Abrus precatorius seeds traditionally used for the treatment of sciatica and alopecia contains the toxic protein, abrin, a Type II Ribosome Inactivating Protein. Ayurveda recommends the use of Abrus seeds after the Shodhana process (detoxification). OBJECTIVE: The current study was aimed at performing the Shodhana process, swedana (boiling) of Abrus precatorius seeds using water as a medium and to evaluate the anti-inflammatory potential of seed extract post detoxification. MATERIALS AND METHODS: Non-detoxified and detoxified extracts were prepared and subsequently subjected to various in vitro and in vivo assays. In hemagglutination assay, the non-detoxified extract shows higher agglutination of RBCs than detoxified extract indicating riddance of toxic hemagglutinating proteins by Shodhana. This was confirmed by the SDSPAGE analysis of detoxified extract revealing the absence of abrin band in detoxified extract when compared to non-detoxified extract. RESULTS: The cytotoxicity assay in HeLa cell line expresses a higher reduction in growth percentage of the cells with non-detoxified extract as compared to detoxified extract indicating successful detoxification. Brine shrimp lethality test indicated the reduction in toxicity index of detoxified extract as compared to non-detoxified extract. Further, the whole body apoptosis assay in zebrafish revealed that percentage of viable cells were greater for detoxified extract than non-detoxified extract. The anti-inflammatory studies using carrageenan induced paw edema model in rats was carried out on the extracts with doses of 100 mg/kg and 200 mg/kg, per oral, where the detoxified extract exhibited significant inhibition of rat paw edema at both the doses comparable to that of Diclofenac sodium. CONCLUSION: Absence of toxicity and the retention of the anti-inflammatory activity of detoxified Abrus seed extract confirmed that the Swedana process is effective in carrying out the detoxification without affecting its therapeutic potential.