pH‐Sensitive Hydrogels as Gastrointestinal Tract Absorption Enhancers: Transport Mechanisms of Salmon Calcitonin and Other Model Molecules Using the Caco‐2 Cell Model

Abstract

The main interest of this work was the investigation of the transport mechanisms of salmon calcitonin through the epithelial cell monolayer in the presence and absence of pH-sensitive hydrogel nanospheres composed of poly(methacrylic acid-grafted-poly(ethylene glycol)) (PMAA-g-EG). For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed. The transport of other macromolecules such as fluorescein sodium, fluorescein isothiocyanate dextran, and (14)C-mannitol were also investigated and compared. Transport experiments were conducted in the apical-to-basolateral direction at 37 and 5 degrees C and from the basolateral-to-apical direction at 37 degrees C. Results revealed that the presence of P(MAA-g-EG) nanospheres increased the transport of paracellularly transported molecules such as (14)C-mannitol and fluorescein isothiocyanate dextran when compared to controls. Fluorescein sodium salt solutions were investigated as an actively transported molecule. The transport of fluorescein was affected by the concentration of PEG chains in the structure. Salmon calcitonin transport was enhanced in the presence of the nanospheres. The comparison of the transport behavior of dextran and calcitonin revealed that the main transport mechanism for salmon calcitonin through epithelial cell monolayers is predominantly paracellular.

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia

“…Cal was thus used as a positive control for paracellular transport. 56 Caf permeation was also assessed as a transcellular positive control with low molecular weight (194.19 Da). 57 Both compounds are physiologically active in the brain.…”

Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

“…Peppas and co-workers prepared complexation polymers which protected proteins such as insulin and calcitonin from possible degradation in the gastric region by the ability of the polymers to respond to changes in pH (32)(33)(34)(35)(36). Complexation hydrogels of poly(methacrylic acid) grafted with poly(ethylene glycol) depicted by the authors as P(MAA-g-EG) were prepared by free radical solution UV-polymerization of methacrylic acid (MAA) and methoxy-terminated poly(ethylene glycol) monomethacrylate (PEGMA).…”

Synthesis, Characterization and In Vivo Efficacy of PEGylated Insulin for Oral Delivery with Complexation Hydrogels

“…In this way, P(MAA-g-EG) can bypass the aggressively degrading environment of the stomach and deliver insulin to the small intestine where there is lower enzymatic activity and increased potential for absorption by the local tissues (6,7,9,10). These hydrogels have also exhibited the ability to inhibit the degradation of insulin in the gastric environment (7,9), bind to the mucus layer of the small intestine (11,12), reduce enzymatic activity in the lumen of the small intestine (6,8), locally and reversibly permeate the tight junctions the epithelial layer (13) and deliver insulin to the bloodstream in a number of in vitro and in vivo tests (10,14,15). The results of previous work with this delivery design has been somewhat promising with bioavailability relative to subcutaneously administered insulin as high as 9.5% (14).…”