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Promoted Antitumor Activity of Myricetin against Lung Carcinoma Via Nanoencapsulated Phospholipid Complex in Respirable Microparticles

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Abstract

Purpose

Myricetin (MYR) flavonoid is well-recognized for its antioxidant, anti-inflammatory and anti-tumor potential. Introducing nanomedicine was the ultimate resort to solve the imperfections of this nutraceutical, namely solubility, stability and delivery issues. The study, thus, aims at developing inhalable microparticles comprising MYR solid lipid nanoparticles (SLNs) for lung cancer therapy.

Methods

A two-step preparation procedure starting with complexation of MYR with the phospholipid Lipoid-S100, followed by nanoencapsulation in Gelucire-based, surfactant-free SLNs was developed. SLNs were characterized in terms of physicochemical properties, MYR loading, release behavior as well as anti-tumor potential and cellular uptake. Respirable microparticles were then obtained by spray drying SLNs with carbohydrate carriers. Their size, flowability and pulmonary deposition pattern were assessed.

Results

Optimized SLNs were 75.98 nm in diameter with a zeta-potential of −22.5 mV, and an encapsulation efficiency of 84.5%. Attempts to ameliorate drug loading implicate MYR-phospholipid complexation (MYR-PH-CPX) prior to its entrapment in SLNs, which ensured 5-fold increase in drug loading. Viability assays were modified to guarantee MYR chemical stability. Superior antitumor activity of MYR-phospholipid-complex and 3-fold reduction in IC50 were accomplished with MYR-SLNs. This could be related to enhanced cellular uptake revealed by confocal imaging and doubled fluorescence intensity. SLNs entrapping MYR-PH-CPX were spray-dried with carbohydrate carriers to produce respirable microparticles. The latter ensured MMAD of 2.39 μm and span index of 1.84, in addition to good flowability and > 80% release over 8 h. Deposition experiments revealed MMAD of 2.77 μm, FPF of 81.23 and EF of 93% indicating particle deposition in the targeted bronchial region.

Conclusions

The study highlights the ability of phospholipid-complex on the nanoencapsulation, cellular uptake and antitumor activity of MYR. Formulation of respirable microparticles gives promises of efficacious therapy of lung carcinoma.

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Abbreviations

Cp:

Compritol 888 ATO

DMEM:

Dulbecco’s Modified Eagle’s Medium

G 39/01:

Gelucire 39/01

G 44/14 :

Gelucire 44/14

G 50/13:

Gelucire 50/13

MYR-PH-CPX:

Myricetin-phospholipid complex

MYR:

Myricetin

PX 407:

Poloxamer 407

SLNs:

Solid lipid nanoparticles

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt

    Noha Nafee & Osama Y. Abdallah

  2. Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, 13110, Safat, Kuwait

    Noha Nafee

  3. Department of Pharmaceutical Sciences, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, Egypt

    Dina M. Gaber

  4. Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt

    Ahmed O. Elzoghby

  5. Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt

    Ahmed O. Elzoghby

  6. Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Ahmed O. Elzoghby

  7. Department of Pharmacology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt

    Maged W. Helmy

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  1. Noha Nafee
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  2. Dina M. Gaber
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Correspondence to Noha Nafee.

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Nafee, N., Gaber, D.M., Elzoghby, A.O. et al. Promoted Antitumor Activity of Myricetin against Lung Carcinoma Via Nanoencapsulated Phospholipid Complex in Respirable Microparticles. Pharm Res 37, 82 (2020). https://doi.org/10.1007/s11095-020-02794-z

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