Nebulised antibiotherapy: conventional versus nanotechnology-based approaches, is targeting at a nano scale a difficult subject?

Abstract

Nebulised antibiotics offer great advantages over intravenously administered antibiotics and other conventional antibiotic formulations. However, their use is not widely standardized in the current clinical practice. This is the consequence of large variability in the performance of nebulisers, patient compliance and a deficiency of robust preclinical and clinical data. Nebulised antibiotherapy may play a significant role in future pulmonary drug delivery treatments as it offers the potential to achieve both a high local drug concentration and a lower systemic toxicity. In this review, the physicochemical parameters required for optimal deposition to the lung in addition to the main characteristics of currently available formulations and nebuliser types are discussed. Particular attention will be focused on emerging nanotechnology based approaches which are revolutionizing inhaled therapies used to treat both infections and lung cancer. Promising carriers such as Trojan-Horse microparticles, liposomes, polymeric and lipid nanoparticulate systems have been investigated and proposed as viable options. In order to achieve site-specific targeting and to optimize the PK/PD balance critical nanoscale design parameters such as particle size, morphology, composition, rigidity and surface chemistry architecture must be controlled. Development of novel excipients to manufacture these nanomedicines and assessment of their toxicity is also a keystone and will be discussed in this review.

Nano-delivery to the lung - by inhalation or other routes and why nano when micro is largely sufficient?

“…As targeted aerosol delivery to the affected lung tissues may both improve therapeutic efficiency and reduce adverse effects, inhaled aerosols are widely used for the treatment of lung diseases such as asthma, COPD, cystic fibrosis, respiratory infection and, more recently, lung cancer [1,3,7,73].…”

“…The features, advantages and drawbacks of each of them are detailed below. It should be kept in mind that no universal system suitable for all applications exist, and different parameters should be considered when choosing a device such as the active agent, the formulation characteristics, the target site, and the pulmonary pathophysiology [13,73]. Indeed, the site and extent of aerosol deposition in the lung is dependent on particle size, velocity and inertia, patient's inspiratory air flow and the inhalation technique.…”

Antibacterial Activity of Thymus vulgaris L. Essential Oil Vapours and Their GC/MS Analysis Using Solid-Phase Microextraction and Syringe Headspace Sampling Techniques

“…For example, nebulised tobramycin, colistin, and aztreonam lysine are commonly used in Europe as inhaled antibiotics against chronic Pseudomonas aeruginosa infections [9]. However, difficulties with implementing optimal nebulisation techniques and the lack of robust clinical data have limited the widespread adoption of aerosol treatments [10][11][12]. Among other reasons, this can be attributed to both particle-related and patient-related factors.…”

Defining a Regulatory Strategy for ATMP/Aerosol Delivery Device Combinations in the Treatment of Respiratory Disease

“…For a nebulizer to support substantial equivalence claims, the device must be characterized in vitro and compared to the in vitro data of the predicate device under the Good Laboratory Practice standards [ 145 ]. Comparison of the released aerosol from the mouthpiece is a performance characteristic which must be evaluated and includes the total emitted mass, dose delivery uniformity, and particle size distribution [ 147 , 148 ].…”