HEC-cysteamine particles: influence of particle size, zeta potential, morphology and sulfhydryl groups on permeation enhancing properties.
Within this study, the influence of particle size and zeta potential of hydroxyethyl cellulose-cysteamine particles on permeation enhancing properties was investigated. Particles were prepared by four different methods namely ionic gelation, spray drying, air jet milling and grinding. Particles prepared by grinding were additionally air jet milled. All particles were characterized in terms of particle size and zeta potential. The transport of fluorescein isothiocyanate-dextran 4 (FD4) across Caco-2 cell monolayers in the presence of these particles and the decrease in transepithelial electrical resistance (TEER) was evaluated. The cytotoxic effect of the particles was investigated using resazurin assay. Nanoparticles displaying a zeta potential of 3.3 ± 1.3 mV showed the highest enhancement of FD4 transport among all particles with a 5.83-fold improvement compared to buffer only. Due to the larger particle size, particles generated by grinding exhibited a lower capability in opening of tight junctions compared to smaller particles generated by air jet milling. In addition, the results of the transport studies were supported by the decrease in the TEER. All particle formulations tested were comparatively non-cytotoxic. Accordingly, the zeta potential and particle size showed a significant impact on the opening of tight junctions and hence could play an important role in the design of hydroxyethyl cellulose (HEC)-cysteamine-based nano- and micro-particles as drug delivery systems.
Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Leopold-Franzens-University Innsbruck, Innsbruck, Austria.
Deni
D
Rahmat
Christiane
C
Müller
Gul
G
Shahnaz
Katharina
K
Leithner
Flavia
F
Laffleur
Mohammad Imran
MI
Khan
Ronny
R
Martien
Andreas
A
Bernkop Schnürch
D001692:Biological Transport; D018938:Caco-2 Cells; D002482:Cellulose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000648:ultrastructure; D055598:Chemical Phenomena; D003543:Cysteamine / Q000009:adverse effects / Q000737:chemistry*; D003911:Dextrans / Q000378:metabolism; D017097:Electric Impedance; D020895:Enterocytes / Q000378:metabolism*; D005079:Excipients / Q000009:adverse effects / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption; D008863:Microspheres; D008956:Models, Chemical; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000737:chemistry*; D013499:Surface Properties; D019108:Tight Junctions / Q000378:metabolism*; D015854:Up-Regulation
D003911:Dextrans; D005079:Excipients; D005456:Fluorescent Dyes; D013438:Sulfhydryl Compounds; C015219:fluorescein isothiocyanate dextran; D003543:Cysteamine; D002482:Cellulose; C002283:hydroxyethylcellulose; D016650:Fluorescein-5-isothiocyanate