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Proniosomal Microcarriers: Impact of Constituents on the Physicochemical Properties of Proniosomes as a New Approach to Enhance Inhalation Efficiency of Dry Powder Inhalers

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Abstract

Proniosomes are free-flowing systems with coating carriers, which developed as a method for improving the drug flow and pulmonary delivery. Extensive research on proniosomes was done to enhance the dry powder inhalers (DPI)’s inhalation performance. This research aimed at studying the impact of lactose-mannitol mixture additives on the proniosome’s physicochemical properties as a method for improving the inhalation efficiency of DPI. Vismodegib has been employed as a compound model. Box–Behnken design has been employed to prepare different proniosomes formulae by incorporating various (A) span 60 concentrations, (B) lactose concentrations and (C) mannitol: total carrier mixture. The measured responses were vesicle size (R1), %release (R2), Carr’s index (R3) and %recovery (R4). The results displayed that R1 and R4 were significantly antagonistic to C and significantly synergistic to both A and B while R2 and R3 were significantly synergistic to C and significantly antagonistic to both A and B. The optimal formula was selected for its aerodynamic behaviour, cytotoxic activity and bioavailability assessment. The optimal formula resulted in better Vismodegib lung deposition, cytotoxic activity and relative bioavailability. This novel formula could be a promising carrier for sustained delivery of drugs via the pulmonary route.

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Abbreviations

DPIs:

Dry powder inhalers

%EE:

Percentage of entrapment efficiency

R2 :

correlation coefficients

Di:

Desirability index

DSC:

Differential scanning calorimetry

TEM:

Transmission electron microscopy

span 60:

sorbitan monostearate

CI:

Carr’s index

IC50:

50% cell viability

MMAD:

Median mass aerodynamic diameter

Cp max :

The maximum drug concentration in plasma

T max :

Time to reach the maximum drug concentration in plasma

t1/2 :

Time to reach half the drug concentration in plasma

K:

Elimination rate constant

MRT:

Mean residence time

AUC:

The area under the curve

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Acknowledgements

The authors would like to thank the staff members of the Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Egypt, for their support for the aerodynamic characterization measurements.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, El-Shahid/Shehata Ahmed Hijaz St., Beni-Suef, Egypt

    Amr Gamal, Ossama M. Sayed, Rasha M. Kharshoum & Heba F. Salem

  2. Clinical Pharmacy Department, Faculty of pharmacy, Beni-Suef University, Beni-Suef, Egypt

    Haitham Saeed

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  1. Amr Gamal
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Correspondence to Heba F. Salem.

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Gamal, A., Saeed, H., Sayed, O.M. et al. Proniosomal Microcarriers: Impact of Constituents on the Physicochemical Properties of Proniosomes as a New Approach to Enhance Inhalation Efficiency of Dry Powder Inhalers. AAPS PharmSciTech 21, 156 (2020). https://doi.org/10.1208/s12249-020-01705-0

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