Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec;29(1):1112-1121.
doi: 10.1080/10717544.2022.2058651.

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

Yogeeta Agrawal  1 , Kiran Patil  1 , Hitendra Mahajan  2 , Mrugendra Potdar  1 , Pratiksha Joshi  2 , Kartik Nakhate  3 , Charu Sharma  4 , Sameer N Goyal  3 , Shreesh Ojha  5
Affiliations

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

Yogeeta Agrawal et al. Drug Deliv. 2022 Dec.

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 23 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 t1/2, AUC0-∞, 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.

Keywords: Entacapone; Parkinson's disease; nanostructured lipid carriers; quality by design.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Structure of Entacapone.
Figure 2.
Figure 2.
Response surface plot showing the effect of variables i.e. total lipid concentration and surfactant concentration over the particle size [A] and entrapment efficiency [B].
Figure 3.
Figure 3.
Scanning electron microscopic (SEM) photograph of Entacapone-loaded NLCs.
Figure 4.
Figure 4.
Particle size and zeta potential of Entacapone-loaded NLCs.
Figure 5.
Figure 5.
DSC overlay thermogram of Entacapone, GMS, physical mixture, and Entacapone NLCs.
Figure 6.
Figure 6.
XRD of plain Entacapone [A] and GMS [B], Physical mixture [C], and Lyophilized Entacapone–NLCs [D].
Figure 7.
Figure 7.
In vitro drug release of free Entacapone and optimized Entacapone-NLC.
Figure 8.
Figure 8.
Drug release kinetics of Entacapone-loaded NLCs.
Figure 9.
Figure 9.
Plasma drug profile of free Entacapone and drug-loaded NLCs in Wistar rats.
See this image and copyright information in PMC

References

    1. Agrawal YO, Mahajan UB, Agnihotri VV, et al. (2021). Ezetimibe-loaded nanostructured lipid carrier based formulation ameliorates hyperlipidaemia in an experimental model of high fat diet. Molecules 26:1485. - PMC - PubMed
    1. Ajiboye AL, Nandi U, Galli M, et al. (2021). Olanzapine loaded nanostructured lipid carriers via high shear homogenization and ultrasonication. Sci Pharm 89:25.
    1. Antonini A, Moro E, Godeiro C, et al. (2018). Medical and surgical management of advanced Parkinson’s disease. Mov Disord 33:900–8. - PubMed
    1. Ashkar A, Sosnik A, Davidovich-Pinhas M. (2021). Structured edible lipid-based particle systems for oral drug-delivery. Biotechnol Adv 54: 107789. - PubMed
    1. Bampidis V, Azimonti G, Bastos MdL, et al. (2020). Safety and efficacy of sodium carboxymethyl cellulose for all animal species. Efsa J 18:26–31. - PMC - PubMed

LinkOut - more resources