Intranasal propranolol hydrochloride-loaded PLGA-lipid hybrid nanoparticles for brain targeting: Optimization and biodistribution study by radiobiological evaluation

Abstract

The present work aimed to load propranolol hydrochloride (PN), a beta-blocking agent with low oral bioavailability, into PLGA-lipid hybrid nanoparticles (PLHNPs) for augmenting its efficacy. PLHNPs contain phospholipid (PC) in addition to PLGA to augment the potential of PLGA nanoparticles in the intranasal delivery and PN avoidance of the blood–brain barrier for the management of migraine. PLHNPs were prepared by single emulsion/ solvent evaporation method and then optimized by applying 2³ full factorial design using PC amount (mg) (X₁), PLGA amount (mg) (X₂), and surface active agent type (X₃) as independent variables, whilst their effect was inspected for entrapment efficiency percent (EE%) (Y₁) and particle size (PS) (Y₂). Design-Expert® was utilized to choose the optimum PLHNPs for more explorations. The optimum PLHNPs formulation (F2) had EE% of 78.00 ± 0.71 %, PS of 104.50 ± 2.04 nm, polydispersity index of 0.429 ± 0.033, and zeta potential of 23.70 ± 0.10 mV. The optimum PLHNPs formulation was stable for up to 90 days. Moreover, it showed a sustained release profile compared to PN solution. It also showed a spherical shape under a transmission electron microscope. The optimized PN-loaded PLHNPs formulation was radio formulated with radiolabeled isotope ([^99mTc]Tc) in maximum radiolabeling yield (91.40 ± 1.85 %) of [^99mTc]Tc-PLHNPs to be used in radiological evaluation for in-vivo biodistribution and brain targeting after oral and intranasal administration. [^99mTc]Tc-PLHNPs showed higher brain targeting (5.80 ± 0.12 % ID/g) with a high brain-to-blood ratio of (2.42 ± 0.14) at 0.5 h after intranasal administration in addition to controlled blood levels and sustained release up to 8 h that confirm the efficacy of PLHNPs for brain targeting.