The development of novel formulations for controlled pulmonary drug delivery purposes has gained remarkable interest in medicine. Although nanomedicine represents attractive concepts for the treatment of numerous systemic diseases, scant information is available on the controlled drug release characteristics of colloidal formulations following lung administration, which might be attributed to the lack of methods to follow their absorption and distribution behavior in the pulmonary environment.In this chapter, we describe the methods of preparation and characterization of drug-loaded polymeric nanoparticles prepared from biodegradable charge-modified branched polyesters, aerosolization of the nanosuspensions using a vibrating-mesh nebulizer, and evaluation of the pulmonary pharmacokinetics (i.e., absorption and distribution characteristics) of the nanoscale drug delivery vehicles following aerosol delivery to the airspace of an isolated lung model. The disclosed methodology may contribute to the design of advanced colloids for the treatment of respiratory disorders.
Inhalation of therapeutic aerosols has a long tradition and is, moreover, regarded as a safe and efficient route of drug administration to the respiratory tract. Especially, the targeting opportunities of this approach are beneficial for the treatment of numerous airway diseases. However, the rapid decay of local drug concentration and the resulting short-term duration of action of conventional medications necessitates several daily inhalations, which is clearly in conflict with a patients' convenience and compliance. Recent progress in pharmaceutical engineering has provided promising drug delivery vehicles (e.g., liposomes, nanoparticles and thermo-responsive preparations) allowing for a sustained release of the encapsulated medication at the target site. Nevertheless, aspects such as generating tailored aerosols from these formulations (including stability during aerosolization) and the choice of biocompatible excipients remain considerable challenges, which need to be addressed in order to optimize inhalation therapy. Therefore, toxicology issues raised by these novel drug delivery vehicles with respect to physicochemical and material properties and biocompatibility are described in this review. This brief overview is intended to serve as a foundation to prompt future advancement in the field of controlled drug delivery to the lungs.
Summary: The solubilization and encapsulation of the weakly soluble protein hemoglobin was investigated at the nanoscale using self‐assembly with the branched polymer polyethyleneimine (PEI), the lipid glycerol monooleate (GMO), and two amphiphilic poly(ethylenglycol) monooleate derivatives with molecular weights 2100 g/mol (MO‐PEG1) and 860 g/mol (MO‐PEG2). The created self‐assembly nanovehicles were analyzed by quasi‐elastic light scattering (QELS) in order to determine their sizes as well as by circular dichroism in order to characterize the protein presence in the nanoobjects. The cationic polymer PEI formed mixed nano‐objects with the protein hemoglobin. The polymer conformation in the nanovehicle was established to be sensitive to dilution, a property that can be essential for the protein release upon administration. The amphiphile MO‐PEG1 was a co‐surfactant in the dispersion of monoglyceride lipid nanoobjects needed for the hemoglobin encapsulation. The amphiphile MO‐PEG2 formed small micelles in the absence of a lipid. The nanoobjects dispersions were studied for their stability on storage and reproducibility.
Sample aging is an alternative to electrolyte supplementation in order to ameliorate the aerosol characteristics of degradable NP formulations when nebulized by vibrating-mesh technology.
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