Oral drug administration is regarded as the most popular, convenient, and widespread mode of administration. It has various benefits over intramuscular, intravenous, and pulmonary delivery, such as painless patient self-administration and high patient adherence [1]. Some therapeutic agents, however, cannot be incorporated into oral dosage forms because of their poor oral absorption and bioavailability [2].

Chronic hypertension is defined as chronically increased arterial blood pressure, which may result in a variety of cardiovascular conditions, including stroke and atherosclerosis [3]. Hence, the control of hypertension is a global health priority [4]. Stage I and stage II hypertension, as well as angina pectoris, were reported to be well managed with lercanidipine HCl (LER), a third-dihydropyridine calcium channel blocker (DHP-CCBs) [5]. Lercanidipine is distinguished by excellent vascular selectivity and persistence in the membranes of smooth muscle cells [6]. Unlike the first and second generations of DHP-CCBs, lercanidipine does not activate the sympathetic nervous system and dilates both the afferent and efferent glomerular arteries while maintaining intraglomerular pressure [7]. Additionally, by increasing the bioavailability of endothelial nitric oxide, lercanidipine reduces kidney damage brought on by angiotensin II and exhibits anti-inflammatory, antioxidant, and anti-atherogenic characteristics [8,9].

Lercanidipine's effectiveness has been proven in patients with various levels of hypertension, in young and old individuals, and in patients with a single episode of systolic hypertension [10]. Lercanidipine exhibits renal protection in individuals suffering from diabetes and kidney problems, with a considerable reduction in microalbuminuria and an improvement in creatinine clearance [11,12]. In comparison to amlodipine and nifedipine, lercanidipine has a favorable safety profile and comes with an extremely low incidence of side effects, particularly ankle edema [13]. In conclusion, lercanidipine has a favorable tolerability profile, a high number of responders/normalized patients, and a prolonged blood pressure-lowering efficacy [14]. Unfortunately, in addition to being unpredictable in terms of its absorption, orally administered LER has only a 10 % absolute bioavailability owing to its presystemic metabolism and low aqueous solubility [15]. Furthermore, the therapeutic efficacy of orally administered LER can be limited by interactions with certain foods and low patient compliance [16]. All of these challenges have indicated the need for a different delivery route capable of transporting LER effectively and acceptably.

Intranasal administration is one route that could be an alternative delivery platform for poorly available oral medicines. For instance, using the nasal route to carry a medication directly into the brain via the olfactory system could reduce dosage-related side effects and bypass the liver's first-pass processing, resulting in enhanced bioavailability and fewer side effects [17,18]. Furthermore, nasal administration is a practical, secure, and noninvasive method of drug administration and also has more rapid effects than other ways, such as oral and transdermal approaches [19].

Naturally, the various benefits of nasal administration have drawn researchers' interest in this method of drug delivery. However, systemic medication distribution via the nasal cavity is significantly hampered by mucociliary clearance [20]. A mucus coating covers the nasal cavity's entire surface [21]. Drugs are quickly removed from their absorbing site by mucociliary clearance. Sneezing, coughing, and hair in the nostrils all significantly lower the amount of particles that can enter the human circulatory system via nose mucosal barrier along with mucociliary clearance [22]. Nasal drug distribution also has drawbacks, such as permanent mucosa damage brought on by formula contents, which isn't true of all medications and is impacted by nasal disorders like allergies [20].

Spanlastic nanovesicles (SNVs) are nonionic surfactant-based vesicles characterized by unique elasticity, fluidity, and deformability. The surfactants employed in them are arranged in the form of a bilayered membrane or shell that entirely surrounds an aqueous core [23]. The SNVs are robust sorbitan ester‒tailored vesicles produced by using edge activators (EAs) to modify standard niosomes within the intended formulation [24]. There has recently been an increase in interest in the use of spanlastics to enhance the ocular [25,26], transtympanic [27], topical and transdermal delivery of numerous medications [[28], [29], [30]]. Spanlastics are non-immunogenic, biodegradable, and harmless vesicular transporters. Additionally, because of their flexibility, they are more beneficial than traditional niosomal dispersions and more chemically resilient than liposomes [31]. The presence of EA, which acts as a destabilizing factor of the lipid membrane and boosts the pliability and penetration of the nanovesicles across cellular membranes, is credited with giving spanlastic vesicles their elastic properties [29]. This allows them to deform and squeeze through various punctures in biological membranes [25].

EAs exert their destabilizing effect by lowering the interfacial tension between the materials that form the shell and the surrounding aqueous media [32]. Because of their extreme deformability, SNVs can be squeezed via intercellular ambits and hence penetrate the phospholipid bilayer of the cell membrane [33]. According to the published research, spanlastics can enhance the effectiveness of medications through a variety of modes of administration [[34], [35], [36]].

A recent advancement in nanovesicle preparation involved the modification of the nanovesicle's surface with a mucoadhesive component to increase the nanovesicle's bioadhesion. The component used was the biodegradable, bioadhesive polymer chitosan, which is widely used in the manufacturing of bioadhesive vesicles due to its capacity to bind with mucin, the primary protein of the nasal mucosal membrane [37]. Additionally, by loosening the tight connections between epithelial cells, chitosan prolongs drug release and improves drug permeability [[38], [39], [40], [41]].

To the best of our knowledge, this was the first attempt to enhance LER bioavailability by loading it into chitosan-grafted spanlastic nanovesicles and administering it via the nasal route. Therefore, the purpose of this study was to determine if bioadhesive spanlastics could effectively distribute LER via the nasal route. The hope was that this method would boost the bioavailability of LER by avoiding the hepatic metabolism and delivering the LER to the systemic circulation.