doi:10.1016/j.ijpharm.2006.10.043 
Copyright © 2006 Elsevier B.V. All rights reserved.
Factors influencing intestinal microparticle uptake in vivo
M. Doyle-McCullougha, 
, 
, S.H. Smytha, S.M. Moyesb and K.E. Carrb
aQueen's University of Belfast, School of Medicine & Dentistry, 71 University Road, Belfast BT7 1NN, United Kingdom
bDepartment of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, United Kingdom
Received 24 August 2006;
revised 23 October 2006;
accepted 28 October 2006.
Available online 9 November 2006.
References and further reading may be available for this article. To view references and further reading you must
purchase this article.
Abstract
The aim of this study is to compare microparticle uptake in animals of different ages, gender and species and at different time points. The 2 μm latex/in vivo in situ model uses the observation of animal responses or post-mortem changes and also particle identification by fluorescence microscopy in nine sequential intestinal segments and secondary sites. The wide size range of animals studied requires particle numbers in tissue compartments to be related to intestinal tissue section area through a circumference measurement. Area under the curve (AUC) data for particles in intestinal tissue are plotted against measurements of intestinal length, allowing comparisons to be made across different ages and species and between males and females. The percentage uptake of administered dose and particle numbers in macerated tissue are also reported. Some parameters, in particular species, do not appear to affect the extent of microparticle uptake, which ranges from 0.12 to 0.32% of the administered dose. Particle uptake does, however, vary with age, being significantly greater in young adult males (7 weeks) than in younger (3 weeks) and older (17 and 52 weeks) age groups. It is concluded that age is more important in determining the extent of uptake than gender or species.
Keywords: Microparticle uptake; Rat small intestine; Age; Species; Time
 |
Fig. 1. Confocal images of propidium iodide stained cryosections of glutaraldehyde fixed small intestine of: (a) young adult male rat, 21 days old, showing villous tip with particles on surface and in the lamina propria, where the particle has caused a tissue tear during sectioning. (b) Young adult male rat, 21 days old, optical slices of the area seen in (a) showing that the particle is within the section, since it is not visible in the first and last levels of the series. (c) Young adult male rat, 21 days old, showing particles within a goblet cell and also at the surface or just inside the apical cytoplasm of another goblet cell. (d) Mid-villus region of 17-week-old rat small intestine, showing particles associated with enterocytes: more particles are visible within the lamina propria of the adjacent villus. (e) Female rat; optical slices showing presence of particle within the section, in a blood vessel in the outer layer of the muscularis externa; the diameter of the particle can be compared with that of the red blood cells within the vessel. (f) Young adult male rat, 21 days old, with one particle in the submucosa and another associated with cryptal epithelium.
Fig. 2. Particle numbers 5, 30 and 90 min after administration in luminal, surface and tissue compartments for small intestinal segments 2 and 8.
Fig. 3. Stacked uptake profiles for four ages of male rats. The vertical line (|) marks the end of the length of the small intestine, with X-axis subunits representing segments 1–9. Total particle numbers for surface and luminal compartments are provided as particles/circumference (14 μm section) and AUC value is for tissue uptake in particles/mm2 all summed for segments 1–9.
Fig. 4. Uptake profiles for three species of young adult males. The vertical line (|) marks the end of the length of the small intestine, with X-axis subunits representing segments 1–9. Total particle numbers for surface and luminal compartments are provided as particles/circumference (14 μm section) and AUC value is for tissue uptake in particles/mm2 all summed for segments 1–9.
Table 1.
Details of experiments, animal groups and samples
* Data for most of these animals were already reported in
Smyth et al. (2005). Samples from one additional animal/group were collected with the 90 min group.
a P is particle fed; C is sterile double-distilled water fed control.
b SI is small intestine; MLN is mesenteric lymph node.
Table 2.
Average number of particles/circumference 14 μm sections/time
Data are for proximal and distal segments of female rat small intestine for three time points, calculated from three sections. Values in brackets indicate standard errors. The data for 5 and 30 min are taken from 6 animals (Smyth et al., 2005): data for the 1 additional animal for each point were inside the range of the values in the table for all tissue, all surface and almost all luminal sites. Data for 90 min are new unpublished figures.
* Indicates significance between 30 and 90 min luminal data. No particles were found in sections from water fed control animals. Data are taken from experiment 1/time/microscopy (
Table 1).
Table 3.
Lengths (cm), section surface areas (mm2) and particles/mm2 (bold text) for all nine segments/age and species
No particles were found in sections from water fed control animals. Data are taken from experiment 3a/age/microscopy and 4a/species/microscopy (Table 1). The surface area measurements are used to convert the particle numbers/circumference section to particles/mm2.
Table 4.
Average number of particles/circumference in 14 μm of sectioned small intestine/age
Data are for 3-week/7-week (bold text)/17-week/52-week-old male rats (n = 6), for all nine small intestinal segments 30 min after particle administration, calculated from 10 sections. Standard error of means is not included as these data are composite figures. Mean small intestinal length for males of 64.8 ± 2.6 cm (3 weeks); 123.7 ± 10.8 cm (7 weeks); 114.5 ± 6.5 (17 weeks); 122.8 ± 5.6 (52 weeks). No particles were found in sections from water fed control animals. Data are taken from experiment 3a/age/microscopy (Table 1).
Table 5.
Variation in dimensions (length, cm, and section area, mm2) and uptake measurements (total uptake; AUC, i.e. particle numbers/section area/intestinal length; percentage uptake)/age and species
Statistical testing was carried out within all groups, significant differences are shown as bold text: seg is segment. No particles were found in sections from water fed control animals. Data are taken from experiment 3a/age/microscopy and 4a/species/microscopy (Table 1).
Table 6.
Average number of particles/circumference in 14 μm of sectioned small intestine/gender
Data are for male (bold text)/female rat (n = 6), for all nine small intestinal segments 30 min after particle administration, calculated from ten sections. Standard error of means is not included as these data are composite figures. Mean small intestinal length for males of 123.7 ± 10.8 cm and 94.2 ± 3.6 cm for females. No particles were found in sections from water fed control animals. Data are taken from experiment 2a/gender/microscopy (Table 1).
Table 7.
Particle numbers per μl of macerated sample for small intestine and mesenteric lymph nodes/age, gender and species
SI is small intestine and MLN is mesenteric lymph node. Percentage of particles taken up relative to administered dose is also given for each group. No particles were found in sections from water fed control animals. Data are taken from experiment 2b/gender/maceration; 3b/age/maceration; 4b/species/maceration (Table 1).
Abstract
Purchase PDF (1460 K)
E-mail Article
Add to my Quick Links
Cited By in Scopus (7)
Purchase PDF (677 K)
