Increasing drug retention in lung tissue through conjugation with polyethylene-glycol
Bayard, Fabrice J.C. (2013) Increasing drug retention in lung tissue through conjugation with polyethylene-glycol. PhD thesis, University of Nottingham.
The pulmonary delivery of drugs is an attractive route of administration because of the large surface area and high permeability of the airway epithelium. The large majority of inhaled drugs are used to manage asthma and Chronic Obstructive Pulmonary Disorder (COPD), such as inhaled corticosteroids and β2-adrenergic receptor agonists. Local delivery of small molecules often results in sub-optimal pharmacokinetics characterised by short absorption times (tmax) and high systemic concentrations (Cmax). Numerous drug delivery strategies have been attempted to increase lung retention time, including drug encapsulation in microspheres, the use of polymeric excipients, or the formation of low solubility drugs. So far, drug conjugation strategies have been limited to decreasing the prodrug solubility. The non-permanent conjugation of small molecules to a large hydrophilic polymer has not been studied for pulmonary delivery. The rationale behind such a strategy is that small molecules are mainly absorbed through the epithelium by passive diffusion, the absorption rates being positively correlated to the drug lipophilicity and molecular weight.
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