Development of <i>in vitro</i> and <i>in vivo</i> evaluation of mucoadhesive in-situ gel for intranasal delivery of vinpocetine

ABSTRACT Alzheimer's disease (AD), which is marked by gradual neuronal decline and subsequent loss of cognitive functions and memory, poses significant treatment challenges. The present study involved the development, <i>in vitro</i>, and <i>in vivo</i> evaluation of a novel intranasal mucoadhesive in-situ gel of vinpocetine (VIN) with the aim to target the brain. An innovative gel formulation composed of poloxamer 407, HPMC E15 LV, and citric acid as a solubilizer was developed by 2³ Factorial Design. The developed optimal formulation exhibited favorable rheological properties as it displayed ideal gelation time (31.6 ± 1.52 sec), optimum gelling temperature (32 ± 1.0 °C), enhanced mucoadhesive strength (6622 ± 2.64 dynes/cm²), prolonged adhesion (7.22 ± 0.57 hrs) compared with the baseline formulation (F18), and improved drug release in 12 hrs (39.59 ± 1.6%). <i>In vivo</i>, pharmacokinetics revealed a significant increase in C_max (∼2-fold) and AUC_0-t (∼2-fold) in the brain with the in-situ intranasal gel compared to the oral route. In the rat model of AD, in-situ intranasal gel demonstrated significantly greater efficacy (<i>p</i> < 0.001) than oral administration in alleviating AD symptoms as evidenced by behavioral and histological studies. Thus, VIN in-situ gel can be safe and noninvasive for nose-to-brain drug delivery.