Pulmonary delivery of antitubercular drugs using spray-dried lipid–polymer hybrid nanoparticles

Abstract

The present study aimed to develop lipid-polymer hybrid nanoparticles (LPNs) for the combined pulmonary delivery of isoniazid (INH) and ciprofloxacin hydrochloride (CIP HCl). Drug-loaded LPNs were prepared by the double-emulsification solvent evaporation method using the three-factor three-level Box-Behnken design. The optimized formulation had a size of 111.81 ± 1.2 nm, PDI of 0.189 ± 1.4, and PDE of 63.64 ± 2.12% for INH-loaded LPN, and a size of 172.23 ± 2.31 nm, PDI of 0.169 ± 1.23, and PDE of 68.49 ± 2.54% for CIP HCl-loaded LPN. Drug release was found to be sustained and controlled at lower pH and followed the Peppas model. The in vitro uptake study in alveolar macrophage (AM) showed that uptake of the drugs was increased significantly if administered in the form of LPN. The stability study proved the applications of adding PLGA in LPN as the polymeric core, which leads to a much more stable product as compared to other novel drug delivery systems. Spray drying was done to produce an inhalable, dry, powdered form of drug-loaded LPN. The spray-dried (SD) powder was equally capable of producing nano-aggregates having morphology, density, flowability and reconstitutibility in the range ideal for inhaled drug delivery. The nano aggregates produced by spray drying manifested their aerosolization efficiency in terms of the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter. The in vivo study using pharmacokinetic and pharmacodynamic approaches revealed that maximum internalization efficiency was achieved by delivering LPN in SD powdered forms by pulmonary route.

Development of dry powder inhaler formulations for drug delivery systems

“…Bhardwaj et al developed isoniazid and ciprofloxacin hydrochloride containing lipid-polymer hybrid nanoparticles using spray drying method for the treatment of tuberculosis. Characterization of DPI was investigated in terms of aerodynamic properties using an eight-stage Andersen Cascade Impactor at 28.3 L/min flow rate for 10 s. When isoniazid loaded DPI and ciprofloxacin hydrochloride loaded DPI results were compared, emitted dose (%), FPF and MMAD values were obtained very close to each other [65]. This shows that the developed DPI production method may be suitable for formulating different active ingredients.…”

“…Lipid-polymer nanoparticles-based DPIs frequently use poly (lactic-co-glycolic acid) as the polymer and lecithin as the lipid source. As particles smaller than 1 µm are exhaled, the nanoparticles are transformed into microscale structures (nanoaggregates or nanocomposites having a theoretical aerodynamic diameter between 1 and 5 µm) to achieve effective aerosolization [63][64][65] (Table 2).…”

Inhalable hybrid nanocarriers for respiratory disorders

“…Hybrid nanoparticles possess good loading efficacy, structural integrity, cell targeting properties, and better cellular affinity. It is also beneficial in drug delivery of both hydrophilic and hydrophobic drugs [7] . Pulmonary administration of nanoparticles also reduces the drug dose to about 5% of the initial dose [8] .…”

Cyclosporine A/porous quaternized chitosan microspheres as a novel pulmonary drug delivery system

“…Drug delivery by the pulmonary provides applicable features including local targeting, circumvention of first-pass hepatic metabolism and rapid onset of action. Based on these characteristics, numerous efforts have been made to design drug delivery by the pulmonary route for local or systemic effect [7][8][9]. However, commercially available inhalable products are mainly rapid release formulations that require the patient to inhale several times every day, thus reducing patient compliance [10].…”