RESUMEN
Mucus layer covers the ocular surface, and soluble mucins are also present in the tear fluid. After topical ocular drug administration, the drugs and formulations may interact with mucus layer that may act as a barrier in ocular drug delivery. In this mini-review, we illustrate the mucin composition of the ocular surface and discuss the influence of mucus layer on ocular drug absorption. Based on the current knowledge the role of mucus barrier in drug delivery is still undefined. Furthermore, interactions with mucus may prolong the retention of drug formulations on the ocular surface. Mucus may decrease or increase ocular bioavailability depending on the magnitude of its role as barrier or retention site, respectively. Mechanistic studies are needed to clarify the role of mucin in ocular drug delivery.
Asunto(s)
Absorción Fisiológica , Barrera Hematoacuosa/metabolismo , Ojo/metabolismo , Glicocálix/metabolismo , Membrana Mucosa/metabolismo , Moco/metabolismo , Farmacocinética , Administración Oftálmica , Animales , Barrera Hematoacuosa/química , Barrera Hematorretinal/química , Barrera Hematorretinal/metabolismo , Conjuntiva/química , Conjuntiva/metabolismo , Córnea/química , Córnea/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/farmacocinética , Ojo/química , Glicocálix/química , Humanos , Aparato Lagrimal/química , Aparato Lagrimal/metabolismo , Mucinas/química , Mucinas/metabolismo , Membrana Mucosa/química , Moco/química , Nanopartículas/química , Permeabilidad , Distribución TisularRESUMEN
The purpose of this study was to quantify gene expression levels of the ATP-binding cassette (ABC) transporter A and C subfamilies ABCA1-A9, and ABCC1-6/Mrp1-6, C10/Mrp7 in mouse retinal vascular endothelial cells (RVEC) using a combination of a magnetic isolation method for mouse RVEC and real-time quantitative PCR analysis. The transcript level of endothelial cell markers, such as CD31, Tie-2, claudin-5, occludin, ABCB1a/mdr1a, and ABCG2, were more than 20-fold higher than those in the non-RVEC fraction, suggesting that RVEC in the RVEC fraction are concentrated at least 20-fold compared with those of the non-RVEC fraction. In the ABCA1 to A9 families, the transcript level of ABCA3 and A9 in the RVEC fraction was 1.2- and 32-fold higher than that in the non-RVEC fraction. Although ABCA3 was expressed in both the RVEC and non-RVEC fractions, A9 is predominantly expressed in the RVEC fraction. In the ABCC1 to C6 and C10 families, the transcript level of ABCC3, C4, and C6 in the RVEC fraction was 27-, 251-, and 242-fold higher, respectively, than that in the non-RVEC fraction, suggesting that ABCC3, C4, and C6 are predominantly expressed in the RVEC. In conclusion, ABCA3, ABCA9, ABCC3, ABCC4, and ABCC6 mRNAs are predominantly expressed at the inner blood-retina barrier (inner BRB) and appear to play a major role in the efflux transport of their substrates at the inner BRB.
