To use rodent models effectively in in-vivo investigations on oral drug and vaccine delivery, the conditions in the gastrointestinal tract must be understood. Some fundamental information is currently unavailable or incomplete. We have investigated the pH, water content and lymphoid tissue distribution along the gastrointestinal tract, as well as the stomach volume, as these were critical to our investigations on pH-responsive drug delivery and colonic vaccination. The observed values were compared with those in man as an indication of the validity of the rodent model. The mouse stomach pH was 3.0 (fed) and 4.0 (fasted), and the corresponding values in the rat were 3.2 (fed) and 3.9 (fasted). The mean intestinal pH was lower than that in man (
Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these in, post-mortem, healthy guinea pigs, rabbits, and the pigs to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 3.1 and 4.4 in guinea pig and pig respectively. In contrast, a very low pH (1.5) was recorded in the fed rabbits. The small intestinal pH was found in the range of 6.4 to 7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51 g, 153 g and 1,546 g respectively. When normalized to the body weight, the guinea pig, rabbit and pig had larger amounts of water compared to man (guinea pig > rabbit > pig > man); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pig < rabbit < pig < man). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig in comparison to man reiterates the crucial importance of correctly selecting animal models for pre-clinical studies.
Sorbitan monostearate, a hydrophobic nonionic surfactant, gels a number of organic solvents such as hexadecane, isopropyl myristate, and a range of vegetable oils. Gelation is achieved by dissolving/dispersing the organogelator in hot solvent to produce an organic solution/dispersion, which, on cooling sets to the gel state. Cooling the solution/dispersion causes a decrease in the solvent-gelator affinities, such that at the gelation temperature, the surfactant molecules self-assemble into toroidal inverse vesicles. Further cooling results in the conversion of the toroids into rod-shaped tubules. Once formed, the tubules associate with others, and a three-dimensional network is formed which immobilizes the solvent. An organogel is thus formed. Sorbitan monostearate gels are opaque, thermoreversible semisolids, and they are stable at room temperature for weeks. The gels are affected by the presence of additives such as the hydrophilic surfactant, polysorbate 20, which improves gel stability and alters the gel microstructure from a network of individual tubules to star-shaped "clusters" of tubules in the liquid continuous phase. Another solid monoester in the sorbitan ester family, sorbitan monopalmitate, also gels organic solvents to give opaque, thermoreversible semisolids. Like sorbitan monostearate gels, the microstructure of the palmitate gels comprise an interconnected network of rodlike tubules. Unlike the stearate gels, however, the addition of small amounts of a polysorbate monoester causes a large increase in tubular length instead of the "clustering effect" seen in stearate gels. The sorbitan stearate and palmitate organogels may have potential applications as delivery vehicles for drugs and antigens.
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