Thermosensitive nasal in situ gels of lipid-based nanosystems to improve the treatment of Alzheimer's disease

Thermosensitive nasal in situ gels are promossing formulations to administer drugs used in the management of Alzheimer's disease (AD). These formulations increase the residence time of the lipid-based nanosystems, improving drug bioavailability, and therapeutic efficacy [1-3].

The purpose of this study was to prepare thermosensitive in situ gels with optimized aqueous dispersions of nanostructured lipid carriers (NLC) and nanoemulsions to improve the residence time of an anticholinesterase drug (RVG) in the nasal cavity and, therefore, its nose-to-brain delivery. Thermosensitive in situ NLC and nanoemulsions gels were developed by the cold technique previously described by Fatouh et al. and Almeida et al. [4, 5]. Poloxamer 407 was used as gelling agent and hydroxypropyl methylcellulose as mucoadhesive polymer. Different concentrations of both polymers were added to the dispersions of NLC and nanoemulsions to optimize the gelation temperature, which was analyzed after 24h of storage at 34ºC, and a concentration of 17% of poloxamer and 0.3% of hydroxypropyl methylcellulose was selected.

The thermosensitive in situ gels of NLC and nanoemulsions were first characterized for particle size, polydispersity index (PDI), zeta potential (ZP), and pH. After that, rheological and textural analyses were performed. The results showed that the prepared formulations had a particle size, PDI, ZP, and pH of, respectively: 141.70±0.40 nm and 146.10±1.73 nm; 0.45±0.00 and 0.43±0.02; -4.06±1.03 mV and -4.09±0.71 mV, 6.60±0.01 and 7.00±0.02, which are all acceptable values for nasal application. Besides, thermosensitive in situ gels of NLC and nanoemulsions showed a non-Newtonian plastic behavior, and the texture parameters viz., compressibility, firmness, and adhesiveness presented desirable values for a nasal gel.

From these results, we conclude that thermosensitive in situ gels of NLC and nanoemulsion can be used to improve the treatment of AD through the nose-to-brain route. However, further in vitro and ex vivo studies should be performed to confirm this application.

References: [1] Zhang, L., et al. Int. J. Pharm, 2020.583:199384; [2] Adnet, T., et al. Pharmaceutics, 2020. 12(3): 251; [3] Alipour, S., et al. Trends Pharmacol Sci, 2020. 6(2): 97-104. [4] Fatouh, A.M., et al. Drug Deliv. 2017. 24(1): 1077-1085; [5] Almeida, H., et al. Curr. Drug Deliv, 2013. 10(6): 753-764.