Formulation and Evaluation of α-Pinene Loaded Self-emulsifying Nanoformulation for In-Vivo Anti-Parkinson's Activity

Abstract

Aim: The aim of the present study was to develop and optimize the self-nanoemulsifying drug delivery system of α-pinene (ALP-SNEDDS) and to evaluate its in-vivo anti-Parkinson’s activity. Background: Different lipid-based drug delivery technologies have been researched to upgrade the bioavailability of such drug candidates and to expand their clinical adequacy upon oral administration. Self-emulsifying drug delivery system (SEDDS) have pulled in expanding interests and, specifically, self-nanoemulsifying drug delivery system (SNEDDS). Objective: The present work was an attempt in order to improve the bioavailability of the ALP via defining the role of self-nanoemulsifying formulations for its neuroprotective effect. Method: Miscibility of the ALP was estimated in various excipient components to select the optimized combination. Self-nanoemulsification, thermodynamic stability, effect of dilution on robustness, optical clarity, viscosity and conductivity tests were performed. The in-vivo anti-Parkinson’s activity of the ALP-SNEEDS formulations were done by using Pilocarpine antagonism induced Parkinsonism in rodents. Behavioural tests like tremulous jaw movements, body temperature, salivation and lacrimation are performed. Result: Two optimized formulation, composed of Anise oil, Tween 80 and Transcutol-HP of Oil: Smix ratio (4:6 and 3:7) were selected. The Smix ratio for both the formulation was 2:1. The particle size was found to consistent with the increase in dilution. The mean negative zeta potential of the formulations was found to be increased with increase in dilution. The TEM images of the formulations reveals spherical shape of the droplet. The in-vitro drug release profile was found to be significant as compared to plain ALP suspension. Conclusion: The results form in-vivo studies indicate that nanosizing and enhanced solubilisation of oral ALP-SNEDDS formulations significantly improved the behavioural activities as compared to plain ALP suspension.

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

“…A small number of SEDDS-based products have already been successfully introduced into the pharmaceutical market, with none of them loading drugs for the treatment of neurological disorders. Until now, several in vivo assays using oral SEDDS have been carried out for neuropharmaceuticals brain targeting [ 4 , 6 , 23 , 24 , 25 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 70 ], but only a few in vivo pre-clinical studies have been reported for IN administration of neurotherapeutics loaded in SEDDS. In fact, only six studies were found that investigated the IN administration of neurotherapeutics loaded in SEDDS: clonazepam [ 45 ], diazepam [ 44 ], and perampanel [ 28 ] for epilepsy treatment; Bdph for glioblastoma treatment [ 4 ]; huperzine A [ 30 ] for Alzheimer’s disease; and naringin [ 5 ] as a neuroprotective for Alzheimer’s and Parkinson’s disease.…”

“…This demonstrates the advantages of using nasal SEDDS rather than a simple nasal solution, the oral route or the invasive IV route for brain delivery of drugs. By analyzing Table 2 , it is noted that, despite the pharmacokinetic evaluation, some authors also performed behavioral studies to compare the efficacy and safety of drugs loaded in SEDDS administered with those of simple solutions, suspensions or commercial preparations of the same drugs [ 4 , 25 , 29 , 31 , 32 , 33 , 46 , 48 , 49 , 50 ]. For the case of glioblastoma treatment, efficacy was directly assessed after oral administration of chlorogenic acid SMEDDS [ 48 ] or the new prodrug 13a-(S)-3-pivaloylocyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) [ 49 ].…”

“…By this pharmacodynamic evaluation, the authors concluded that curcumin-SMEDDS had a better effect on improving memory, cognition, and locomotion, with a decrease in serum cortisol levels, compared with those receiving pure curcumin [ 50 ]. For treating Parkinson’s disease, Srivastava et al [ 29 ] and Borkar et al [ 33 ] also used behavioral studies to evaluate the therapeutic advantages of, respectively, α-pinene and dipalmitoyl apomorphine loaded in SEDDS. Compared with oral suspension, α-pinene-SNEDDS triggered a higher attenuation in tremulous jaw movements in the hypothermic effect and the inhibition of salivation and lacrimation, all induced by pilocarpine administration [ 29 ].…”

“…For treating Parkinson’s disease, Srivastava et al [ 29 ] and Borkar et al [ 33 ] also used behavioral studies to evaluate the therapeutic advantages of, respectively, α-pinene and dipalmitoyl apomorphine loaded in SEDDS. Compared with oral suspension, α-pinene-SNEDDS triggered a higher attenuation in tremulous jaw movements in the hypothermic effect and the inhibition of salivation and lacrimation, all induced by pilocarpine administration [ 29 ]. To study the effects of dipalmitoyl-apomorphine-loaded SEDDS, the 6-hydroxydopamine-lesioned rat model was applied.…”

Neuroprotective effect of α‐pinene self‐emulsifying nanoformulation against 6‐OHDA induced neurotoxicity on human SH‐SY5Y cells and its in vivo validation for anti‐Parkinson's effect

“…Data were analyzed using one-way and two-way analysis of variance followed by and Transcutol-HP (20%) as a drug, carrier oil, surfactant, and cosurfactant, respectively. [40] The formulation was further subjected to in vitro and in vivo safety and efficacy assessment.…”