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. 2022 Aug 8;29(1):2671-2684.
doi: 10.1080/10717544.2022.2110996.

Surface-tailoring of emulsomes for boosting brain delivery of vinpocetine via intranasal route: in vitro optimization and in vivo pharmacokinetic assessment

Hibah M Aldawsari  1   2 , Shaimaa M Badr-Eldin  1   2 , Nourah Y Assiri  1 , Nabil A Alhakamy  1   2   3   4 , Anna Privitera  5 , Filippo Caraci  5   6 , Giuseppe Caruso  5   6
Affiliations

Surface-tailoring of emulsomes for boosting brain delivery of vinpocetine via intranasal route: in vitro optimization and in vivo pharmacokinetic assessment

Hibah M Aldawsari et al. Drug Deliv. .

Abstract

Vinpocetine (VNP), a semisynthetic active pharmaceutical ingredient, is used for oral management of cerebrovascular diseases because of its ability to enhance the blood flow to the brain. However, despite that, the therapeutic application of VNP is restricted due to its reduced bioavailability and diminished brain levels that could be attributed to its low aqueous solubility, short half-life, and presystemic metabolism exposure. Accordingly, the goal of this work was to explore the ability of surface-tailored intranasal emulsomes to boost brain delivery of the drug. A 3221 factorial design was implemented to explore the impact of phospholipid (PL) to solid lipid weight ratio, PL to cholesterol molar ratio, and type of solid lipid on vesicle size, zeta potential, drug entrapment, and release efficiency of the new developed VNP emulsomes. Tailoring of the optimized emulsomal surface formulation was performed using either cationization or PEGylation approaches to boost blood-brain barrier penetration. The pharmacokinetic assessment in rats showed significantly improved bioavailability of VNP emulsomal formulations compared to the oral market product. Additionally, surface-tailored emulsomes exhibited significantly higher brain levels compared to the optimized emulsomes. Based on these findings, the proposed surface-tailored emulsomes could be considered as a promising platform for achieving high brain levels of VNP following intranasal administration.

Keywords: PEGylation; Vinpocetine; brain delivery; cationization; pharmacokinetics; surface-tailored intranasal emulsomes.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Response 3D surface plot for the influence of PL:SL weight ratio (X1), PL:CH molar ratio (X2), and SL type (X3) on VS (Y1) of VNP emulsomes. (A) SL type (Tripalmitin), (B) SL type (Tristearin), (C) PL:CH (4:1), and (D) PL:SL (2:1).
Figure 2.
Figure 2.
Response 3D surface plot for the influence of PL:SL weight ratio (X1), PL:CH molar ratio (X2), and SL type (X3) on ZP (Y2) of VNP emulsomes. (A) SL type (Tripalmitin), (B) SL type (Tristearin), (C) PL:CH (4:1), and (D) PL:SL (2:1).
Figure 3.
Figure 3.
Response 3D surface plot for the influence of PL:SL weight ratio (X1), PL:CH molar ratio (X2), and SL type (X3) on EE% (Y3) of VNP emulsomes. (A) SL type (Tripalmitin), (B) SL type (Tristearin), (C) PL:CH (4:1), and (D) PL:SL (2:1).
Figure 4.
Figure 4.
Response 3D surface plot for the influence of PL:SL weight ratio (X1), PL:CH molar ratio (X2), and SL type (X3) on RE24h (Y4) of VNP emulsomes. (A) SL type (Tripalmitin), (B) SL type (Tristearin), (C) PL:CH (4:1), and (D) PL:SL (2:1).
Figure 5.
Figure 5.
TEM micrographs of (A) optimized VNP emulsomes E12, (B) SA surface-tailored emulsomes E19, and (C) MPEG-DSPE surface-tailored emulsomes E24. Magnification = 22500X.
Figure 6.
Figure 6.
Release profile of (A) SA and (B) MPEG-DSPE surface-tailored emulsomes in PBS (pH 6.8) at 35 ± 0.5 °C compared to the optimized emulsomes (E12). Results are presented as mean (n = 3) ± SD.
Figure 7.
Figure 7.
Mean VNP concentration in (A) plasma and (B) brain following the intranasal administration of VNP optimized emulsomes (E12), SA surface-tailored emulsomes (E19) and MPEG-DSPE surface-tailored emulsomes (E24) compared to the orally administered market tablets in rats. Results are presented as mean (n = 6) ± SD.
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References

    1. Abdel-Mottaleb MM, Lamprecht A. (2011). Standardized in vitro drug release test for colloidal drug carriers using modified USP dissolution apparatus I. Drug Dev Ind Pharm 37:178–84. - PubMed
    1. Ahirrao M, Shrotriya S. (2017). In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting. Drug Dev Ind Pharm 43:1686–93. - PubMed
    1. Ahmed TA, Badr-Eldin SM, Ahmed OA, Aldawsari H. (2018). Intranasal optimized solid lipid nanoparticles loaded in situ gel for enhancing trans-mucosal delivery of simvastatin. J Drug Delivery Sci Technol 48:499–508.
    1. Al Asmari AK, Ullah Z, Tariq M, Fatani A. (2016). Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil. DDDT 10:205–15. - PMC - PubMed
    1. Aldawsari HM, Ahmed OAA, Alhakamy NA, et al. (2021). Lipidic nano-sized emulsomes potentiates the cytotoxic and apoptotic effects of raloxifene hydrochloride in mcf-7 human breast cancer cells: factorial analysis and in vitro anti-tumor activity assessment. Pharmaceutics 13:783. - PMC - PubMed

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