Pulmonary delivery of nanosized alendronate for decorporation of inhaled heavy metals: formulation development, characterization and gamma scintigraphic evaluation.

CONTEXT: Medical management of heavy metal toxicity including radioactive ones is the cause of concern because of their increased use in energy production, healthcare and mining. As inhalation is one of the primary routes for internalization, a formulation is needed to trap metal(s) at the portal of entry itself.

OBJECTIVE

Objective was to formulate and characterize a nanonized dry powder inhaler (DPI) formulation of alendronate sodium as potential inhalable antidote for chelating metal toxicants.

METHODS

In vitro binding studies of alendronate with respect to seven non-radioactive heavy metals were carried out using UV-spectroscopy and HPLC. Nanonizing of alendronate particles was achieved by antisolvent precipitation using Pluronic-F68 as stabilizer. Characterization was done with the help of SEM, TEM FT-IR, XRD, DSC, NMR spectroscopy and PSD studies. In vitro and in vivo pulmonary deposition studies were carried out using gamma scintigraphy, followed by a limited pharmacokinetic study in humans.

RESULTS

In vitro binding studies confirmed the chelating action of alendronate. Anderson cascade impaction showed that nano-alendronate exhibited significantly higher respirable fraction (58.25 ± 1.32%) compared to the micronized form (28.7 ± 0.59%). Scintigraphy results showed significant increase in the alveolar deposition of drug post-nanonizing.

CONCLUSION

Results strongly indicate the role of nano-alendronate DPI as potential inhalable antidote for neutralizing heavy metal toxicity, including radio-metal contamination.