Design and In Vitro Evaluation of Cyclodextrin-Functionalized Albumin Nanoparticles for Intranasal Carbamazepine Brain Delivery.

Background/

Objectives

Poor aqueous solubility and limited nasal permeability remain key challenges in the intranasal delivery of carbamazepine. In this study, biocompatible bovine serum albumin nanoparticles functionalized with sulfobutyl-β-cyclodextrin (SβCD-BSA NPs), comprising individually cytocompatible components with confirmed physical interactions), were formulated for intranasal delivery of carbamazepine (CBZ).

Methods

The ethanolic desolvation method was utilised for the preparation of the nanoparticles, with the functional moiety incorporated during nanoparticle preparation. The effects of different molar ratios of SβCD-BSA and different ethanol volume ratios were studied. For crosslinking, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), a non-toxic crosslinker, was utilised. To determine the role of the SβCD, two preparation samples were formulated, with and without SβCD.

Results

The formulation without SβCD incorporation had a mean particle size of 125 ± 0.64 nm, polydispersity index (PDI) of 0.34, encapsulation efficiency (EE%) of 61.5 ± 1.40%, and drug-loading ratio (DL%) of 31.9 ± 1.50%. Conversely, the SβCD-functionalized formulation showed a mean particle size of 128 ± 2.12 nm, PDI of 0.21 ± 0.03, EE of 64.6 ± 0.35%, and DL of 34.28 ± 1.60%. Statistical analysis revealed that the incorporation of SβCD resulted in a statistically significant increase in both DL% and EE% (p < 0.05). Conversely, the observed differences in particle size and PDI were not statistically significant (p > 0.05). This addition provides precise context regarding the comparability of the formulations while highlighting SβCD's functional benefits in solubility and permeation. The interaction between CBZ and SβCD-BSA was confirmed using Fourier-transform infrared spectroscopy. Lastly, the prepared formulations were characterised by their physicochemical attributes and in vitro biopharmaceutical studies. It was discovered that SβCD plays a dual role, enhancing the solubility of CBZ in one scenario while promoting its nasal permeation, suggesting its potential use in epilepsy treatment.

Conclusions

These findings highlight the potential of SβCD-BSA NPs as a versatile pharmaceutics platform for the intranasal delivery of poorly soluble CNS drugs.