Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA

Formulation of pH responsive peptides as inhalable dry powders for pulmonary delivery of nucleic acids

“…On the contrary, spray freeze drying involves multiple steps; liquids are first sprayed into a cryogen such as liquid nitrogen and the droplets, which are frozen immediately, are transferred into a freeze dryer to allow the sublimation of ice, resulting in the formation of highly porous particles. Although both methods can produce inhalable dry powders and have been investigated to produce nucleic acid formulations for pulmonary delivery, the majority of these formulations used polymers and lipids as non-viral vectors [27][28][29][30][31][32] while much less work has been done to investigate the preparation of inhalable powders of nucleic acids with a peptide-based delivery vector.…”

Engineered PLGA nano- and micro-carriers for pulmonary delivery: challenges and promises

“…This can be achieved by biodegradable polymer carriers. [52,[62][63][64] Poly(lactic-co-glycolic acid) carriers in drug delivery and their potential for inhalation Among synthetic biodegradable polymers, thermoplastic aliphatic poly(ester)s, PLGAs, have generated tremendous research interest due to their excellent biocompatibility as well as the possibility of tailoring their biodegradability by varying composition (lactide/glycolide ratio), molecular weight and chemical structure (i.e. capped and uncapped end-groups).…”

“…Hepatitis B surface antigen [80] Dry powders High mucosal immune response in the lungs Rifampicin [81] Dry powders Sustained plasma therapeutic drug levels Drug persistence in lung tissue and cells Nano-embedded microparticles siRNA [64] Dry powders Preservation of siRNA structural integrity Efficient in vitro gene silencing No cytotoxicity (H1299 cells) TAS- 103 anticancer drug [82] Dry powders Enhanced cytotoxicity against A549 cells High local drug concentration Tobramycin [83] Dry powders…”

“…[97] These technologies have demonstrated a great potential also in the development of dry powders for protein delivery, with particular regard to mucosal vaccination, [80,98] and short interference RNA (siRNA) delivery. [64] Although current literature data suggest the potential of PLGA particles for prolonged drug delivery in the lung, their use for inhalation is still embryonic and presents some shortcomings. In particular, a huge amount of work has still to be produced on clearance mechanisms and persistence in vivo that may considerably limit the benefit of sustained-release inhalation therapy.…”

“…Anyway, in vitro cytotoxicity studies have shown that native PLGA has no manifest toxicity against healthy lung macrophages, [99] CF bronchial cells [100] or lung carcinoma cell lines. [64] Furthermore, the proinflammatory potential of PLGA nanoparticles has been recently investigated in vivo and results suggest that biodegradable nanoparticles are safer than non-biodegradable polystyrene particles [101] and do not induce lung tissue damage, [102] also up to 10 days. [71] Nonetheless, chronic toxicological data on PLGA particles are still poor and demand for further studies.…”