Ex Vivo Characterization of Particle Transport in Mucus Secretions Coating Freshly Excised Mucosal Tissues

Abstract

Sustained drug delivery to mucosal surfaces has the potential to improve the effectiveness of prophylactic and therapeutic treatments for numerous diseases and conditions, including inflammatory bowel disease, sexually transmitted diseases, cystic fibrosis, glaucoma, dry eye and various cancers. Sustained delivery systems such as nanoparticles can be useful for mucosal delivery, but recent work suggests they should penetrate the rapidly cleared mucus barrier that overlies all mucosal epithelia to achieve uniform distribution on epithelial surfaces and enhanced residence time. Thus, it is important to evaluate mucus-penetrating ability of nano-sized delivery systems in preclinical animal studies, and for administration to humans. We describe a simple ex vivo method to visualize and quantify nanoparticle transport in mucus on fresh mucosal tissues. Using this method in murine models, we observed variations in the mucus mesh at various anatomical locations, as well as cyclical variations that may have implications for mucosal delivery.

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

“…Consider the heterogeneity of mucus pore sizes 40 , we have also constructed a model system composed of cross-linked polymer network with random pore size (See Methods for details) to represent mucin fibers, as shown in Fig. 7a.…”

Mucus as a Barrier to Drug Delivery – Understanding and Mimicking the Barrier Properties

“…different mucosal surfaces from mice was investigated and compared. The particles were mucus-penetrating, and as they were assumed not to interact with the mucus, the study illustrated the steric barrier of mucus [17]. It was found that the diffusion of 100 nm particles was more restricted in colonic and tracheal tissue than in the small intestinal mucosal tissue, whereas the diffusion was least restricted in oestrus-phase vaginal tissue [17].…”

“…Human mucus is usually isolated from the female genital tract or as sputum from patients with cystic fibrosis. However, it is important to be aware of possible implications related to the mucus source, for example the varying viscosity of cervicovaginal mucus during the oestrous cycle [17] or the abnormal high DNA content and viscosity of cystic fibrosis sputum [6]. Animal mucus can be obtained from all mucosal sites and is usually isolated from larger animals as pigs and horses to obtain adequate quantities.…”

Preparation of Nanoscale Pulmonary Drug Delivery Formulations by Spray Drying

“…The main bronchi then bi-and also trifurcate into smaller bronchi and bronchioles, until the terminal bronchioles appear to show sac-like structures (approximately generation [16][17]. With these so-called respiratory bronchioles begins the gas-exchanging respiratory zone (generation [17][18][19][20][21][22][23], which mainly comprises the alveolar ducts and alveolar sacs (i.e. alveoli; approximately 500 million per adult lung).…”

“…Whereas the cross-sectional surface of the airways (generation 0-16) is only a few square meters, the surface area increases exponentially in the alveolar region (generation [17][18][19][20][21][22][23] to about 75-140 m 2 [ 8 ]. Via the conducting zone, the inspired air is rapidly transported from the central to the peripheral lung by turbulent and laminar fl ow, while it is decelerated to diffusive movement in the transition to the respiratory zone to facilitate the gas exchange [ 9 ].…”