In vitro evaluation of inhalable isoniazid-loaded surfactant liposomes as an adjunct therapy in pulmonary tuberculosis.
In this study, exogenous pulmonary surfactant was evaluated as an inhalable drug carrier for antitubercular drug isoniazid (INH). Isoniazid-entrapped liposomes of dipalmitoylphosphatidylcholine (DPPC) (the most abundant lipid of lung surfactant and exogenous surfactant) were developed and evaluated for size, drug entrapment, release, in vitro alveolar deposition, biocompatibility, antimycobacterial activity, and pulmonary surfactant action. Isoniazid-entrapped DPPC liposomes were about 750 nm in diameter and had entrapment efficiency of 36.7% +/- 1.8%. Sustained release of INH from DPPC liposomes was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger exhibited approximately 25-27% INH deposition in the alveolar chamber upon one minute nebulization using a jet nebulizer. At 37 degrees C, the formulation had better pulmonary surfactant function with quicker reduction of surface tension on adsorption (36.7 +/- 0.4 mN/m) than DPPC liposomes (44.7 +/- 0.6 mN/m) and 87% airway patency was exhibited by the formulation in a capillary surfactometer. The formulation was biocompatible and had antimycobacterial activity. The isoniazid-entrapped DPPC liposomes could fulfill the dual purpose of pulmonary drug delivery and alveolar stabilization due to antiatelectatic effect of the surfactant action which can improve the reach of antitubercular drug INH to the alveoli.
School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
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D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D000327:Adsorption; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D002460:Cell Line; D003167:Complement Activation; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D007538:Isoniazid / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use*; D008422:Materials Testing; D051379:Mice; D008826:Microbial Sensitivity Tests; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D013499:Surface Properties; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D008081:Liposomes; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D007538:Isoniazid