Spanlastics as a Potential Approach for Enhancing the Nose-To-Brain Delivery of Piperine: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Management of Epilepsy

Abstract

The present study delineates the preparation of piperine-loaded spanlastics (PIP-SPL) to improve piperine (PIP) solubility, bioavailability, and permeation through nasal mucosa for intranasal delivery. PIP-SPL was formulated using the thin-film hydration method and optimization was performed using Box–Behnken design (BBD). PIP-SPL optimized formulation (PIP-SPLopt) was characterized for polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential, and in vitro PIP release. For further evaluation, blood–brain distribution study, transmission electron microscopy (TEM), nasal permeation study, and confocal scanning laser microscopy (CLSM) were performed withal. The PIP-SPLopt presented spherical and sealed shape vesicles with a small vesicle size of 152.4 nm, entrapment efficiency of 72.93%, PDI of 0.1118, and in vitro release of 82.32%. The CLSM study unveiled that the developed formulation has greater permeation of PIP across the nasal mucosa in comparison with the PIP suspension. The blood–brain distribution study demonstrated higher Cmax and AUC0–24h of PIP-SPL via the intranasal route in comparison to PIP-SPL via oral administration. The in vivo study revealed that the PIP-SPL has good antiepileptic potential in comparison with the standard diazepam, which was evinced by seizure activity, neuromuscular coordination by rotarod test, biochemical estimation of oxidative stress markers, and histopathological studies. Furthermore, nasal toxicity study confirm that the developed PIP-SPL formulation is safer for intranasal application. The current investigation corroborated that the prepared spanlastic vesicle formulation is a treasured carrier for the PIP intranasal delivery for the management of epilepsy.

Application of QbD‐based approach to the development and validation of an RP‐HPLC method for simultaneous estimation of pregabalin and naringin in dual‐drug loaded liposomes

“…The RBF was placed in a desicator for 24 h. The dried film was hydrated in a water–PRG solution for 1 h before being stored in the refrigerator to achieve adequate swelling. The obtained dispersion was probe sonicated for 4 min with a titanium probe ultra sonicator (UP 100 H, Hielscher Ultrasonics GmbH, Berlin) and then characterized for polydispersity index (PDI), entrapment efficiency and vesicle size (Adin, Gupta, Rashid, et al, 2023; Gupta, Adin, Aqil, Mujeeb, & Sultana, 2022a; Gupta, Adin, Rashid, et al, 2023).…”

“…The RBF was placed in a desicator for 24 h. The dried film was hydrated in a water-PRG solution for 1 h before being stored in the refrigerator to achieve adequate swelling. The obtained dispersion was probe sonicated for 4 min with a titanium probe ultra sonicator (UP 100 H, Hielscher Ultrasonics GmbH, Berlin) and then characterized for polydispersity index (PDI), entrapment efficiency and vesicle size(Adin, Gupta, Rashid, et al, 2023;Gupta, Adin, Aqil, Mujeeb, & Sultana, 2022a;Gupta, Adin, Rashid, et al, 2023).2.8.2 | Characterization of prepared PRG-NRN nanoliposomesThe vesicle size and PDI of the developed PRG-NRN liposomes were estimated using a Zetasizer (Malvern Instruments, Worcestershire, UK) after diluting the sample with Mill-Q water (50 times) at 25 ± 1 C in triplicate at a scattering angle of 90 C(Gupta, Adin, Aqil, Mujeeb, & Sultana, 2022a).2.8.3 | Percentage drug entrapment efficiency and percentage drug loading The entrapment efficiency of liposomes was evaluated using ultracentrifugation. The samples were stored at 40 C overnight before being centrifuged at 20,000 rpm for 1 h at 40 C (REMI, cooling centrifuge, Mumbai, India).…”

Application of exosomes as nanocarriers in cancer therapy

“…Exosome, as a nano-delivery platform, could be loaded with nucleic acids for targeted delivery into the body for gene expression, which overcomes the limitations of current gene therapy delivery technology. 158 PTT and PDT are two effective cancer treatment modalities, which have attracted widespread attention because of their high selectivity and noninvasiveness. 159 However, it is difficult to completely eradicate solid tumors with PTT/PDT alone.…”

Formulation and Characterization of Hesperidin-Loaded Transethosomal Gel for Dermal Delivery to Enhance Antibacterial Activity: Comprehension of In Vitro, Ex Vivo, and Dermatokinetic Analysis

“…The observed increment in % EE as the concentration of phospholipid increases might be attributed to the increase in domain size of the bilayer ensuing from the formation of a higher quantity of TE vesicles. This, in turn, allows for a greater capacity for HSD entrapment within the TE vesicles [33]. The efficiency of the transethosomal system is significantly impacted by ethanol as well; raising the concentration of ethanol will enhance entrapment efficiency.…”