Nano-Liposomal Dry Powder Inhaler of Amiloride Hydrochloride

Abstract

The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7.4 containing carriers (lactose/sucrose/mannitol), and glycine as anti-adherent. The resultant dispersion was spray dried. The spray dried powders were characterized and in vitro drug release studies were performed using phosphate buffer saline pH 7.4. In vitro and in vivo drug pulmonary deposition was carried out using Andersen Cascade Impactor and by estimating drug in bronchial alveolar lavage and lung homogenate after intratracheal instillation in rats respectively. Nano-liposomes were found to have mean volume diameter of 198 +/- 15 nm, and 57% +/- 1.9% of drug entrapment. Mannitol based formulation was found to have low density, good flowability, particle size of 6.7 +/- 0.6 microm determined by Malvern MasterSizer, maximum fine particle fraction of 67.6 +/- 0.6%, mean mass aerodynamic diameter 2.3 +/- 0.1 microm, and geometric standard deviation 2.4 +/- 0.1. Developed formulations were found to have prolonged drug release following Higuchi's Controlled Release model and in vivo studies showed maximal retention time of drug of 12 hrs within the lungs and slow clearance from the lungs. This study provides a practical approach for direct lung delivery of Amiloride Hydrochloride encapsulated in liposomes for controlled and prolonged retention at the site of action from dry powder inhaler. It can provide a promising alternative to the presently available nebulizers in terms of prolonged pharmacological effect, reducing systemic side effects such as potassium retention due to rapid clearance of the drug from lungs in patients suffering from cystic fibrosis.

Surfactant-based drug delivery systems for treating drug-resistant lung cancer

“…Along with some pulmonary therapies, nanoparticulate systems have established numerous benefits in conditions of defending the drug from deterioration and continuous release of drug at extended duration of time. For pulmonary delivery, nanoparticles and liposomes are used to carry anticancer moieties but having some disadvantages mainly the major limitations of these systems are alteration during nebulization, biodegradability, drug outflow and drug-related unfavorable conditions (Bonomi et al, 2000;Chougule et al, 2006). Paclitaxel is one more new drug for treatment in NSCLC which reports 20-25% rate in metastatic patients (Hande, 1998).…”

Hydrogels for Controlled Pulmonary Delivery

“…The percentage of drug entrapped in the liposomes, as an example, ranges from 55 to 80% and may even reach 90% with different ratios of lipids [6,[15][16][17]. Liposomes have been the most commonly used and investigated vehicles for the controlled release of drugs for pulmonary delivery due to their biocompatibility, safety profile and ability to avoid induction of an immune response.…”

Nanomedicine and Drug Delivery Strategies for Treatment of Genetic Diseases

“…For instance, the thick lung sputum encountered in CF patients is a major obstacle for effective penetration of classical inhaled therapeutics, hindering access to the underlining epithelial layer. Encapsulation of antibiotics within liposomes modified with amiloride hydrochloride has been shown to force water retention and reduce viscosity of the sputum, resulting in enhanced release and effects (Chougule, et al, 2006). Liposomes modified with the bioadhesive metal, gallium, improved delivery of antibiotics in the CF airways, permitting reduction of the administered dose by an order of magnitude compared to the naked antibiotic (Halwani, et al, 2008).…”