In vitro and in vivo characterization of Entacapone-loaded nanostructured lipid carriers developed by quality-by-design approach

Abstract

Entacapone, a reversible catechol-o-methyl transferase inhibitor, is used to enhance the action of dopamine agonists by reducing their metabolism and the ‘Wearing-off’ effects associated with long-term use in the treatment of Parkinson's disease. It is used as an adjunct to levodopa/Carbidopa therapy. Due to limited dissolution and first-pass clearance, it suffers low and variable bioavailability issues. To overcome this problem, the present study aims to explore the potential of nanostructured lipid carriers (NLCs) for the delivery of Entacapone. The Quality by Design (QbD) approach was used for the systematic development of NLCs. The 2 3 full factorial designs were investigated using Design-Expert®11 software. The three independent variables namely content of total lipid (X1), surfactant (X2), and sonication time (X3) were optimized against two responses namely particle size and entrapment efficiency. The optimized NLCs were characterized for their size, surface morphology, entrapment efficiency, drug release, thermal and crystallographic studies. In-vivo pharmacokinetic studies in Entacapone-loaded NLCs showed an increase in t 1/2 , AUC 0–∞ , MRT compared to free drug. The reduction in elimination (Kel) depicts the prolonged action of Entacapone by loading in NLCs. The results displayed Entacapone-loaded NLCs have promising potential for oral delivery and enhanced therapeutic effect which otherwise was a major issue.

Cod liver oil nano-structured lipid carriers (Cod-NLCs) as a promising platform for nose to brain delivery: Preparation, in vitro optimization, ex vivo cytotoxicity & in vivo biodistribution utilizing radioiodinated zopiclone

“…The negative effect of increasing sonication time on EE % was similarly reported after piperine NLCs formulation ( Zafar et al, 2021 ). Also, comparable results were declared by Agrawal et al ( Agrawal et al, 2022 ) who found that EE% of entacapone in the formulated NLCs decreased with increasing sonication time.…”

Entacapone Nanoemulsion: Formulation Design, Optimization, and Evaluation

“…Inadequate membrane permeability, insu cient aqueous solubility in gastrointestinal uids, and the rst-pass effect can all contribute to suboptimal bioavailability [12][13][14]. According to the biopharmaceutics classi cation system [15][16][17][18][19][20], Entacapone is categorized as a class IV medication. Reports indicate that nanosized formulations improve the permeability and solubility of water while also preventing rst-pass effects.…”

Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: interplay between nuclear factor-kappa β and cathepsin B

“…Up till now, no perfect treatment exists for management of PD and therapy is mainly focusing on the relief of symptoms [ 4 ]. The current treatment includes the use of dopamine agonists (levodopa) and monoamine oxidase (MAO) inhibitors.…”

“…The current treatment includes the use of dopamine agonists (levodopa) and monoamine oxidase (MAO) inhibitors. Nevertheless, as the disease worsens, the efficacy of the conventional therapy decreases producing end-of-dose adverse effects called wear-off symptoms characterized by the recurrence of both motor and non-motor manifestations [ 4 ]. Recently, the focus on discovering phytomedicines has been growing considerably as a method of finding safer alternatives to synthetic drugs.…”