Geophila repens phytosome-loaded intranasal gel with improved nasal permeation for the effective treatment of Alzheimer's disease

Abstract

Geophila repens (L.) I.M. Johnst is a creeping herb with good anti-cholinesterase activity and has been used traditionally in India to improve memory and intelligence for many years. The antioxidant activity of the ‘methanolic extract of the leaves of Geophila repens' (MEGR) was determined and found to be high, possibly due to the presence of phenolic compounds, flavonoids, and triterpenoids. The permeation of phytoconstituents through the blood–brain barrier is a challenging factor in the development of phytoformulation for the treatment of Alzheimer's disease (AD). To overcome these limitations, ‘Geophila repens phytosome-loaded intranasal gel’ (MEGR-PG) with enhanced permeation properties through the nasal route to the brain was developed. Here, transcutol was used as permeation enhancer and hydroxypropyl methylcellulose as a gelling agent. For the development of MEGR-PG, a screened phytosome (MEGR: soy phosphatidylcholine, 1: 2) with a particle size of 444.93 ± 25.24 nm, PDI value of 0.358 ± 0.012, spherical morphology, encapsulation efficiency of 51.88 ± 1.025% with an immediate in vitro release of 45.84 ± 5.6% at 60 min followed by a maintenance period of up to 480 min was used. MEGR-PG exhibited significant in vitro nasal mucosa permeation without causing skin irritation. Furthermore, MEGR-PG exhibited a similar proportion of acetylcholinesterase inhibition (97.87 ± 6.84%) in comparison to donepezil (97.17 ± 4.86%) but was greater than MEGR (69.86 ± 5.68%), and it also accelerated angiogenesis, which shows potential to modify the cognitive behaviour of AD patients. In addition, the brain targeting effect of MEGR-PG has been confirmed by a preclinical in vivo imaging study. As a result, MEGR-PG is a promising treatment option for AD patients.