Nanomedicine, Volume IIA: Biocompatibility

© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003 Mechanical Peristaltogenesis and Mucosacompatibility

Will colonic nanorobots trigger diarrhea? The mechanical movements of medical nanorobots should not stimulate adverse biological responses during the traversal of mucosal membranes. For example, mucosal surfaces in the stomach and small intestine contain emetogenic mechanoreceptors [2433], and the mechanical stimulation of esophageal [3725] or intestinal [3726] mechanosensors can elicit peristalsis. But shear forces generated during luminal wall locomotion can be held low enough to avoid nausea and emesis (Section Colonic peristalsis may be initiated by the passage of roughage through the colon [3727-3730] or by mechanical brush strokes applied directly to the mucosal tissue [3731], but the shear forces generated by nanorobot mechanical activities may be held below the threshold required to stimulate diarrhea. This threshold has not yet been precisely measured in humans, but it is known that the peristaltic threshold for marmoset ileum is <1000 N/m2 [3733], about 2700 N/m2 for canine gut wall [3734] and for feline small bowel [3735], and that the distension pressure threshold to induce peristalsis in human esophagus is 1500-1900 N/m2 [3702].* (The mechanical stimulation threshold to activate peristalsis in chicken ureters ranges from 770-9330 N/m2 [3732].) Interestingly, mechanical sensory impulses (e.g., air or ~0.3 cm3 water injection) from the pharynx actually inhibit esophageal peristalsis [3736].

* Human esophageal peristaltic pressure is normally 8100-10,200 N/m2 depending upon position [3737] with >4000 N/m2 needed to properly propel a swallowed bolus [3738], and esophageal sphincter pressure is 1790 N/m2 [3739]. Spontaneous jejunal contractions have been measured as 4700 N/m2 [3740]. Colonic wall tension is typically ~5000 N/m2 but can rise as high as 106 N/m2 in ileus patients, higher than the maximum contraction capacity of the large intestine’s muscle system (~5 x 105 N/m2) [3741]. Mechanical destructive forces of the gastrointestinal tract are sufficient to crush test pills having crushing strength of 1.2-1.89 N when swallowed by humans, or 3.2 N in dogs [5017].

Although unlikely to trigger peristalsis, nanorobot mechanical activities may slightly increase mucus secretions from mucosal surfaces. For example, mechanical stimulation of the feline gastric mucosa doubles the rate of submucosal gland secretions [3742]. In rat, adherent mucus is 5-500 microns thick over the gastroduodenal mucosa [3743]. Particles instilled in the lungs, including inert dusts [3744], cause increased numbers and activity of alveolar macrophages and an increased mucus flow rate [3745-3747]. Rapidly adapting receptors throughout the respiratory tract from the nose to the bronchi respond to mechanical stimuli, producing additional airway mucus secretion along with cough and bronchoconstriction [3748]. Particles [3749] or tubes [3750] placed in the nose cause increase nasal mucus flow and mechanical sinusitis. Mechanical stimulation of the nose, nasopharynx and larynx increases tracheal mucus output in the cat [3751]. Mucociliary cilia beat most strongly in the vicinity of a particle due to direct tactile stimulation [3752].


Last updated on 30 April 2004