In vitro and in vivo local tolerability of a synergistic anti-tuberculosis drug combination intended for pulmonary delivery.

A drug combination, vancomycin (VAN) plus tetrahydrolipstatin (THL), has demonstrated an effective synergistic action in vitro against Mycobacterium tuberculosis (Mtb). The poor oral bioavailability of VAN and THL and the predominant tropism of Mtb infection to the lungs make their pulmonary administration very attractive. To evaluate their local tolerability, bronchial cells, alveolar cells and monocytes were exposed to concentrations around and above their minimal inhibitory concentration (MIC).

Preclinical tolerance evaluation of the addition of a cisplatin-based dry powder for inhalation to the conventional carboplatin-paclitaxel doublet for treatment of non-small cell lung cancer.

Despite the advances in targeted therapies and immunotherapy for non-small cell lung cancer (NSCLC) patients, the intravenous administration of carboplatin (CARB) and paclitaxel (PTX) in well-spaced cycles is widely indicated for the treatment of NSCLC from stage II to stage IV. Our strategy was to add a controlled-release cisplatin-based dry-powder for inhalation (CIS-DPI-ET) to the conventional CARB-PTX-IV doublet, administered during the treatment off-cycles to intensify the therapeutic response while avoiding the impairment of pulmonary, renal and haematological tolerance of these combinations. The co-administration of CIS-DPI-ET (0.

The combination of an innovative dry powder for inhalation and a standard cisplatin-based chemotherapy in view of therapeutic intensification against lung tumours.

Cisplatin is one of the most commonly used chemotherapy in lung cancer despite its high nephrotoxicity leading to an administration only every 3-4 weeks. This study is the first report of a preclinical investigation of therapeutic intensification combining a cisplatin dry powder for inhalation (CIS-DPI) with an intravenous (iv) cisplatin-based treatment. CIS-DPI with 50% cisplatin content (CIS-DPI-50) was developed using lipid excipients through scalable processes (high-speed and high-pressure homogenization and spray-drying).

Pulmonary and renal tolerance of cisplatin-based regimens combining intravenous and endotracheal routes for lung cancer treatment in mice.

Despite recent advances, platinum-based chemotherapy (partially composed of cisplatin, CIS) remains the backbone of non-small-cell lung cancer treatment. As CIS presents a cumulative and dose-limiting nephrotoxicity, it is currently administered with an interruption phase of 3-4 weeks between treatment cycles. During these periods, the patient recovers from the treatment side effects but so does the tumour.