Modification of Disodium Cromoglycate Passage Across Lung Epithelium In Vitro Via Incorporation into Polymeric Microparticles

Haghi, Mehra; Salama, Rania; Traini, Daniela; Bebawy, Mary; Young, Paul M.

doi:10.1208/s12248-011-9317-2

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…Calu-3 cells are most commonly used for the assessment of pulmonary permeability because they reached higher TEER values than measured in the rabbit airways and showed good correlation of permeability values with drug absorption from the rat lung in vivo [ 5 – 8 ]. Furthermore, drug release from disodium cromoglycate (DSCG)/polyvinyl alcohol (DSCG/PVA) microparticles in Calu-3 cells showed good correlation to suitable models [ 9 ]. Calu-3 cells are good models because they show similar transporter expression to respiratory cells [ 10 , 11 ]; protein expression of human lung tissue is highest for the organic cation transporter OCTN1, followed by multidrug resistance protein 1 (MRP1), breast cancer resistance protein 1 (BCRP1), ATP-binding cassette sub-family G member 2 (ABCG2), and organic anion transporter OATP2B1.…”

Section: Introductionmentioning

confidence: 99%

Permeation of Therapeutic Drugs in Different Formulations across the Airway Epithelium In Vitro

et al. 2015

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BackgroundPulmonary drug delivery is characterized by short onset times of the effects and an increased therapeutic ratio compared to oral drug delivery. This delivery route can be used for local as well as for systemic absorption applying drugs as single substance or as a fixed dose combination. Drugs can be delivered as nebulized aerosols or as dry powders. A screening system able to mimic delivery by the different devices might help to assess the drug effect in the different formulations and to identify potential interference between drugs in fixed dose combinations. The present study evaluates manual devices used in animal studies for their suitability for cellular studies.MethodsCalu-3 cells were cultured submersed and in air-liquid interface culture and characterized regarding mucus production and transepithelial electrical resistance. The influence of pore size and material of the transwell membranes and of the duration of air-liquid interface culture was assessed. Compounds were applied in solution and as aerosols generated by MicroSprayer IA-1C Aerosolizer or by DP-4 Dry Powder Insufflator using fluorescein and rhodamine 123 as model compounds. Budesonide and formoterol, singly and in combination, served as examples for drugs relevant in pulmonary delivery.Results and ConclusionsMembrane material and duration of air-liquid interface culture had no marked effect on mucus production and tightness of the cell monolayer. Co-application of budesonide and formoterol, applied in solution or as aerosol, increased permeation of formoterol across cells in air-liquid interface culture. Problems with the DP-4 Dry Powder Insufflator included compound-specific delivery rates and influence on the tightness of the cell monolayer. These problems were not encountered with the MicroSprayer IA-1C Aerosolizer. The combination of Calu-3 cells and manual aerosol generation devices appears suitable to identify interactions of drugs in fixed drug combination products on permeation.

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Section: Introductionmentioning

confidence: 99%

Permeation of Therapeutic Drugs in Different Formulations across the Airway Epithelium In Vitro

et al. 2015

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“…The characteristics of drug release from dispersed systems are strongly influenced by the biological environment whereby interactions of particles with biological components, such as phospholipids and protein, could significantly alter the release rate of the drug. Therefore, in vitro models of the airway epithelium are being utilised as representative models of the lungs for studying the impact of formulation on respiratory release profiles [18][19][20]. In such studies, air interfaced airway epithelial cells, such as Calu-3 cells [18,21], are typically used to model the respiratory mucosal surface, and a device for delivering a pharmaceutically-relevant aerosol, such as the twin stage impinger, is used to administer the formulation.…”

Section: Introductionmentioning

confidence: 99%

In vitro and ex vivo methods predict the enhanced lung residence time of liposomal ciprofloxacin formulations for nebulisation

Ong

Benaouda

Traini

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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Liposomal ciprofloxacin formulations have been developed with the aim of enhancing lung residence time, thereby reducing the burden of inhaled antimicrobial therapy which requires multiple daily administration due to rapid absorptive clearance of antibiotics from the lungs. However, there is a lack of a predictive methodology available to assess controlled release inhalation delivery systems and their effect on drug disposition. In this study, three ciprofloxacin formulations were evaluated: a liposomal formulation, a solution formulation and a 1:1 combination of the two (mixture formulation). Different methodologies were utilised to study the release profiles of ciprofloxacin from these formulations: (i) membrane diffusion, (ii) air interface Calu-3 cells and (iii) isolated perfused rat lungs. The data from these models were compared to the performance of the formulations in vivo. The solution formulation provided the highest rate of absorptive transport followed by the mixture formulation, with the liposomal formulation providing substantially slower drug release. The rank order of drug release/transport from the different formulations was consistent across the in vitro and ex vivo methods, and this was predictive of the profiles in vivo. The use of complimentary in vitro and ex vivo methodologies provided a robust analysis of formulation behaviour, including mechanistic insights, and predicted in vivo pharmacokinetics.

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“…The cell layer was then harvested for analysis of the drug inside the cells. The method has been described previously by Haghi et al [3,18]. Briefly, the cells were harvested using trypsin EDTA solution and lysed using Cell lytic and protease inhibitor cocktails.…”

Section: In Vitro Cell Deposition Studiesmentioning

confidence: 99%

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Haghi

Bebawy

Colombo

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tTwo solution-based pressurised metered dose inhaler (pMDI) formulations were prepared such that they delivered aerosols with identical mass median aerodynamic diameters, but contained either beclomethasone dipropionate (BDP) alone (glycerol-free formulation) or BDP and glycerol in a 1:1 mass ratio (glycerol-containing formulation). The two formulations were deposited onto Calu-3 respiratory epithelial cell layers cultured at an air interface. Equivalent drug mass ($1000 ng or $2000 ng of the formulation) or equivalent particle number (1000 ng of BDP in the glycerol-containing versus 2000 ng of BDP in the glycerol-free formulation) were deposited as aerosolised particles on the air interfaced surface of the cell layers. The transfer rate of BDP across the cell layer after deposition of the glycerol-free particles was proportional to the mass deposited. In comparison, the transfer of BDP from the glycerol-containing formulation was independent of the mass deposited, suggesting that the release of BDP is modified in the presence of glycerol. The rate of BDP transfer (and the extent of metabolism) over 2 h was faster when delivered in glycerol-free particles, 465.01 ng ± 95.12 ng of the total drug (20.99 ± 4.29%; BDP plus active metabolite) transported across the cell layer, compared to 116.17 ng ± 3.07 ng (6.07 ± 0.16%) when the equivalent mass of BDP was deposited in glycerol-containing particles. These observations suggest that the presence of glycerol in the maturated aerosol particles may influence the disposition of BDP in the lungs.

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Modification of Disodium Cromoglycate Passage Across Lung Epithelium In Vitro Via Incorporation into Polymeric Microparticles

Cited by 5 publications

References 28 publications

Permeation of Therapeutic Drugs in Different Formulations across the Airway Epithelium In Vitro

Permeation of Therapeutic Drugs in Different Formulations across the Airway Epithelium In Vitro

In vitro and ex vivo methods predict the enhanced lung residence time of liposomal ciprofloxacin formulations for nebulisation

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

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