Parkinson's disease (PD) is a rapid neurodegenerative disorder of central nervous system (CNS caused by the reduction in level of dopamine or loss of dopaminergic neuron in substantia nigra pars compacta of the midbrain [1]. In the PD deposition of intraneuronal protein is called lewy bodies. The principal component of the Lewy bodies is aggregated α-synuclein, approximately PD affects 6.1 million population globally, compared by the population which affected in 1990 which was nearby 2.5 million [1,2]. PD is the second most common neurodegenerative disease among the entire world with prevalence of 0.3 % of progressive movement disorders [3]. In the majority of populations, genetic causes related to known Parkinson's disease genes explain 3–5 % of the heritable risk of Parkinson's disease, whereas 90 genetic risk variations explain 16–36 % of the heritable risk of non-monogenic Parkinson's disease [4].

Esculin hydrate (ESH) is an active substance in coumarin derivatives which belongs to family Hippocastanoideae and the plant is Aesculus hippocastanum linn [3,5]. ESH widely exists in range of fruits, vegetables, and herbs with antioxidant activity and free radical scavenging properties. ESH shows significant anti-Parkinson effects by reducing the level of reactive oxygen species (ROS) in intracellular region, and also enhances superoxide dismutase (SOD) level and it protects mitochondrial membrane potential, restores glutathione (GSH) level. Thus, the above effectiveness indicates that ESH is a potential candidate which shows neuroprotective effects in PD. ESH also shows antioxidant and antiapoptotic properties [1,5,6]. The Intranasal delivery acts as promising approach for targeting of ESH in the brain via olfactory and trigeminal pathways. These pathways avoid the hepatic metabolism and bypass Blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCSF), presystemic metabolism to enhance its brain uptake, this route enhances the effects at low therapeutic dose [7,8]. It has been observed the administration of drug to be a potential pathway for nose to brain therefore targeting directly to CNS. This route is non-invasive and provides rapid therapeutic activity due to having the large surface area of nasal mucosa thereby increasing patient compliance, convenience and comfort [9,10]. There are many lipid based nano formulation which have shown higher therapeutic efficacy by giving intranasal delivery [11,12]. Among these the nanoliposomes found to be very effective nano carrier to enhance permeability and reduce drug dose [13]. The nanoliposomes owing to its nontoxic, non-immunogenic, biodegradable character and structural resemblance to the nasal mucosal membrane [14]. Nanoliposomes have been predicted to be even more efficient for carrying cargo across the BBB due to their optimized size, shape and surface coating [15,16].

In situ gel is a peculiar dosage form that has lately been used for intranasal administration of drugs. In comparison to other liquid nasal formulations, nasal in situ gels are administered as low viscosity solutions into the nasal cavity, and upon contact with the nasal mucosa, the polymer changes conformation, producing a gel, which not only prolongs the contact time between the drug and the absorptive sites within the cavity, but also slowly and continuously releases the drug. The utilization of temperature as a stimulus is prevalent in polymer systems that responds to environmental factors. The insitu gelling systems exhibit a liquid state within a temperature range of 20°–25 °C, and subsequently undergo a phase transition to a gel state upon exposure to body fluids at a temperature range of 35°–37 °C, which is attributed to a temperature-induced gelation process. A phase transition from sol to gel is exhibited by an in situ gel that is sensitive to temperature, occurring at a critical temperature denoted as either the lower critical solution temperature (LCST) or upper critical solution temperature (UCST) [17].

The present study intends to prepare and optimized ESH loaded NLs by the taking of independent variables, such as phospholipid 90G (X1), cholesterol (X2), and sonication time (X3). The optimization of liposomes has been done by taking into account the dependent variables of vesicle size (Y1), entrapment efficiency (Y2), and Polydispersity index (Y3). In addition, the optimized formulation went through evaluation for its antioxidant activity using the DPPH assay, pH measurement, confocal laser scanning microscopy (CLSM), and nasal permeation study.