In vitro testing of flash-frozen sublingual membranes for storage and reproducible permeability studies of macromolecular drugs from solution or nanofiber mats.

Pavel Berka,Karel Berka,Denisa Stránská,Pavel Doležal,Vladimír Semecký

doi:10.1016/j.ijpharm.2019.118711

Pavel Berka, Karel Berka + Show 3 more

Open Access

https://doi.org/10.1016/j.ijpharm.2019.118711

Copy DOI

Abstract

Sublingual drug delivery allows systemic delivery of drug without difficulties connected with the gastrointestinal pathway. We developed a new simple protocol for easy-to-use processing and storage of porcine sublingual mucosal membrane for in vitro studies using "flash freezing" in liquid nitrogen. All the dextrans used as mucosal membrane integrity and permeability markers permeated only slowly through sublingual mucosa illustrating usability both the "fresh" and "flash frozen" sublingual membranes whereas conventional cold storage "frozen" membranes have shown significantly higher permeabilities for macromolecules due to the sustained damage. The permeability values were too low to expect dextrans to be potential carriers at this context. To test albumin as a drug carrier we compared FITC-albumin permeation from solutions vs. nanofiber mats donors. To increase the amounts and prolong the transport, we manufactured nanofiber mats loaded with fluorescently marked albumin using well-scalable electrospinning technology. Nanofiber mats have allowed albumin passage through the sublingual membrane in similar amounts as from the pure artificial saliva solution. Since salivary washout strictly limits the duration of liquid dosages, nanofiber mats may thus permit prolonged sublingual administration.

Highlights

IntroductionSublingual and buccal drug systemic administration has been accepted as a potentially efficient alternative route for fast drug delivery or controlled delivery of small molecule drugs for extended periods (Harris and Robinson, 1992) and has been mentioned as a promising route for some biomacromolecules (e.g. peptides, proteins, nucleotides, enzymes, hormones, vaccines) (Castro et al, 2015; Junginger et al, 1999; Kraan et al, 2014)
Sublingual and buccal drug systemic administration has been accepted as a potentially efficient alternative route for fast drug delivery or controlled delivery of small molecule drugs for extended periods (Harris and Robinson, 1992) and has been mentioned as a promising route for some biomacromolecules (Castro et al, 2015; Junginger et al, 1999; Kraan et al, 2014)
The “fresh” sublingual mucosal membranes obtained from the local slaughterhouse upon further treatment with sodium azide were limited in time to run the tests within 8h post mortem of the animal donors

Summary

Introduction

Sublingual and buccal drug systemic administration has been accepted as a potentially efficient alternative route for fast drug delivery or controlled delivery of small molecule drugs for extended periods (Harris and Robinson, 1992) and has been mentioned as a promising route for some biomacromolecules (e.g. peptides, proteins, nucleotides, enzymes, hormones, vaccines) (Castro et al, 2015; Junginger et al, 1999; Kraan et al, 2014) This route has in principle several advantages over conventional oral drug delivery as it avoids the acidic environment and the enzymatic cleavage in the gastrointestinal tract together with hepatic first-pass metabolism. A short onset of concentration of unchanged drug in peripheral blood and shortened blood way of the drug to CNS has been proven since 150 years ago (Murrell, 1879)

Objectives

Methods

Results

Conclusion