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Preclinical Models for Pulmonary Drug Delivery
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Jibriil P. Ibrahim, Robert J. Bischof, Michelle P. McIntosh
In humans, pulmonary drug delivery is performed via direct drug administration orally into the lungs during normal respiratory inhalation. Replicating this mechanism is not straightforward in animal models. Breathing behavior differs between species, with rabbits, guinea pigs, rats, and mice all obligate nasal breathers, compared to larger animals and humans, who breathe via the mouth or nose and mouth (Allen et al. 2009). This can create challenges during pulmonary drug delivery studies. The current methods that are available for administering pulmonary drug formulations into the lungs of animals are limited in their representation of human delivery systems and can be classified based on their passive or active route of administration (Table 30.3).
In Vivo Measurements of Lung Dose
Published in Hans Bisgaard, Chris O’Callaghan, Gerald C. Smaldone, Drug Delivery to the Lung, 2001
Mark L. Everard, Myrna B. Dolovich
Most drug delivery systems currently used to treat pulmonary disease were developed and introduced into clinical practice long before assessments of pulmonary drug delivery were undertaken. The pharmaceutical companies have seen little reason to improve on the current devices, utilizing technology that is many decades old, because the current systems do produce useful therapeutic responses and are relatively safe (“therapeutic index”) if used effectively.
Pulmonary delivery of resveratrol-β-cyclodextrin inclusion complexes for the prevention of zinc chloride smoke-induced acute lung injury
Published in Drug Delivery, 2022
Wanmei Wang, Yan Liu, Pan Pan, Yueqi Huang, Ting Chen, Tianyu Yuan, Yulong Ma, Guang Han, Jiahuan Li, Yiguang Jin, Fei Xie
Pulmonary drug delivery is a noninvasive method to deliver drugs to damaged lung tissues or improve systemic absorption from the lung (Walenga & Longest, 2016). The ideal therapeutic way of lung diseases is pulmonary drug delivery, involving asthma (Chandel et al., 2019), chronic obstructive pulmonary disease (Wallin et al., 2018), pneumonia (Li et al., 2017), ALI (Zhang et al., 2021), and pulmonary fibrosis (Hu et al., 2018). Currently, the major types of pulmonary delivery strategies include pressurized metered-dose inhalers, nebulizers, dry powder inhalers (DPIs), and soft mist inhalers (Peng et al., 2016). DPIs are composed of portable solid powders. The advantages of DPIs include high drug loads, portability, propellant-free, and good stability (Zhang et al., 2020). However, the development of DPI formulations is a challenge for many drugs because of their high-dose needs and improper physicochemical properties.
Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension
Published in Expert Opinion on Drug Delivery, 2020
Ali Keshavarz, Hossam Kadry, Ahmed Alobaida, Fakhrul Ahsan
The second important feature that influences pulmonary drug delivery is the pharmacokinetics of the inhaled drug. Olschewski et al. showed the serum half-life of iloprost was much shorter than the half-life of the pulmonary vasodilatory effects exerted by this drug, suggesting that the inhaled iloprost caused prolonged local vasodilation not reflected by the serum levels [115]. Several mechanisms may explain this observation. First, perivascular lung tissue (pulmonary artery cells, alveolar lining layer, and interstitial space) may trap a percentage of iloprost following inhalation, and this fraction may possess a longer half-life than the systemic iloprost because it is not exposed to the catabolic enzyme in the lower lung. Second, since the interstitium of the lung alveolar and lining layer are small spaces, even a low quantity of drug result in high local concentrations inducing vasorelaxation of PAs. In summary, the ideal vasodilator therapeutic formulation would be cost-effective, safe, and selective to the pulmonary vasculature.
Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro–in silico lung deposition results
Published in Drug Development and Industrial Pharmacy, 2019
Edit Benke, Árpád Farkas, Imre Balásházy, Piroska Szabó-Révész, Rita Ambrus
Drugs (e.g. antibiotics) can be delivered via the pulmonary route for the purpose of achieving local and systemic effects. This type of drug delivery has many advantages. For example, it should be noted that by circumventing the gastrointestinal tract, the drugs reach the Cmax value in the blood within approximately 1–3 min [15]. By avoiding the first-pass effect of the liver and the enzymatic inactivation of the gastrointestinal system as metabolic pathways, the use of lower doses of active agents is sufficient to induce the same therapeutic effect. Thus, the side effects profile could be modified. In addition, pulmonary drug delivery is a noninvasive therapeutic procedure, which does not cause pain or tissue damage [16,17]. However, at present, only three inhaled antibiotics (tobramycin, aztreonam, and colistimethate (sodium)) are on the market [18]. The use of the dry powder inhalers (DPIs) offers outstandingly many benefits: propellant-free, easy to use, portability, increased stability, less need for patient coordination, etc. [19–21].