Optimization of Modified Poly (Glycerol Adipate) Nanoparticles for Pulmonary Drug Delivery

Ramy Said-Elbahr^{1, 2}, Vincenzo Taresco³ , Giuseppe Mantovani¹, Snow Stolnik¹ & Cynthia Bosquillon¹

¹University of Nottingham, School of Pharmacy, University Park, Nottingham, NG7 2RD, United Kingdom

²Ain Shams University, Faculty of Pharmacy, African Union Organization St., Abbassia, Cairo, 11566, Egypt ³University of Nottingham, School of Chemistry, University Park, Nottingham, NG7 2RD, United Kingdom

Summary

Pulmonary drug delivery is largely used for the localized treatment of lung diseases but suffers from various limitations, some of which could be overcome by polymeric nanoparticles. Unfortunately, few polymers have been deemed compatible with the inhaled route. Poly (glycerol adipate) (PGA), a green enzyme-synthesized biodegradable polymer, offers several advantages over traditional polymers for pulmonary drug delivery purposes. However, modification of its chemical structure is necessary to obtain solid polymers with a high glass transition temperature (T_g) and thus, enable the formulation of modified PGA nanoparticles into micron-sized inhalable powders by spray-drying. PGA was modified with N-acetyl-tryptophan (NAT) using a simple Steglich esterification reaction. The polymers obtained were thoroughly characterised to monitor the effect of NAT % substitution on their T_g values. The PGA polymers were formulated into nanoparticles by nanoprecipitation in presence of different surfactants and the nanoparticles were characterized using dynamic light scattering. PGA was successfully coupled to NAT to obtain solid powder polymers that demonstrated T_g values >40^oC, with a positive correlation between T_g and NAT % substitution observed. The nanoparticle formulations showed hydrodynamic diameters <120 nm, narrow size distributions (PDI <0.2) and negative zeta potential values. Furthermore, they could be sterically stabilized by all the surfactants tested. Thus, modified PGA-NAT nanoparticles are promising candidates for pulmonary delivery. However, future work is needed to confirm that PGA biodegradability and safety on lung cells are preserved upon its chemical modification.

Key Message

PGA polymers offer advantages over traditional polymers to overcome their limitations for pulmonary delivery. Modification of PGA using N-acetyl-tryptophan altered its physicochemical properties producing more solid polymers with glass transition temperatures >40^oC, rendering the formulation of its nanoparticles into inhalable dry powders conceivable.