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 Transepithelial Penetration

Past studies [6173] have shown that the percutaneous penetration of passive microspheres is a function of particle diameter. In more recent studies, Tinkle et al [6174] studied the penetration of size-selected fluorospheres (dextran beads) into postmortem human skin using laser confocal microscopy. They found that beads as large as 0.5-1 micron in diameter can penetrate the stratum corneum and reach the epidermis, and occasionally even the dermis (possibly deep enough for lymphatic system uptake), if the skin is flexed, as at the wrist; >50% of samples showed this activity after 1 hour of flexing. Lademann et al [6175] found that ~0.1 micron titanium dioxide particles used in sunscreen lotions penetrated into the hair follicles of the skin, with <1% of the applied particle concentration found in any given follicle. But in the interfollicular areas the deepest layers of the stratum corneum (and the viable skin tissues below) were devoid of penetrating particles even after repeated applications; microparticles were found only in the areas of the pilosebaceous orifices.

The careless penetration of nanorobots through human skin (Section 9.5.2) could potentially create microscopic perforations through which microbes (e.g., as in cellulitis) and undesirable environmental substances could enter the body and cause disease. (T.G. Wilson notes that with gingival inflammation, which almost everyone has, the epithelium around the tooth becomes quite porous and bacterial entry into the connective tissues and bloodstream is common.) Other pathological conditions associated with numerous and frequent epithelial penetrations include the development of deeply pigmented or discolored skin associated with an excess of skin penetrations by body lice (pediculosis corporis, aka. vagabond’s disease or vagrant’s disease) [3755] and the granulomatous “stylosome” (stalk-mouth) that rises up from the skin in an attempt to wall off burrowing chiggers [3755, 3756]. These results may be avoided by employing exterior lipophilic coatings on the nanorobot (Section to encourage close nanorobot-tissue contact during transit, followed by active breach-sealing procedures (Section once histopenetration is complete.

However, it appears unlikely that lymphatic or other fluids could exude from the body through unsealed epidermal transit holes created by medical nanorobots. The time-averaged interstitial pressure in subcutaneous tissue is 0.8-5 mmHg [3753, 3754], with mean value ~1.4 mmHg (Section Even taking the highest pressure and assuming no tissue self-sealing, internal fluids can overcome surface tension at the fluid-air interface and begin to ooze from pores only if those pores are larger than ~60-600 microns in diameter (Section 9.2.4). Most medical nanorobots and their transit holes should be much smaller than this, and any microholes in soft tissue should rapidly plug or reseal. R. Smigrodzki agrees that “the size of the nanorobots is so small that a channel produced by the robot actively traversing the skin should spontaneously seal within a very short time, unless extreme stretch forces are applied.”

Similar considerations may apply to the transepithelial penetration of nanorobots through stomach, intestinal, or bladder walls lined with cells having tight occluding junctions. Hemorrhage and perforation are two common complications of gastric and duodenal ulcers. Underlying tissues may then suffer chemical irritation by gastric acids and digestive enzymes. Gastric or duodenal perforations develop in 5% of ulcer patients. Such perforations result in chemical peritonitis and could also lead to bacterial peritonitis that causes sudden, severe generalized abdominal pain. Gas intrusion causes the presence of free intraperitoneal air (usually not itself pathological) in 75% of all cases [2421]. However, in the resting stomach a viscous protective layer of bicarbonate-rich mucus adheres closely to the surface of the underlying gastric epithelium. Gastric contents cannot pass into the tissues along unsealed nanorobot transit holes through the gastric epithelium as long as the thick alkaline mucus layer is maintained intact. It has already been noted that nanorobot-sized particles up to ~10-15 microns in diameter normally pass out of the small intestine into lymphatic tissues (i.e., Peyer’s patches) without incident (Section Nanorobotic perforation of the wall of the bacteria-rich colon could potentially introduce gut flora into the bloodstream or surrounding tissues – although R. Smigrodzki notes that gut microbes commonly reach the bloodstream even during straining at stool, so the very small number that might be introduced during nanorobot transit should not be problematic. Lipophilic coatings and breach-sealing protocols could again be employed here, as in dermal histopenetration. Bowel necrosis and intestinal infarction are unlikely if no blood vessels are broken or occluded.

The risk of mechanical damage due to epithelial laceration by aerial nanorobots has already been described in Section Vision loss from corneal abrasions is due to changes in many layers of the cornea. According to Sano et al [3757], abrasions severe enough to mechanically remove cells from the corneal epithelium would also cause massive enlargement of mitochondria in the underlying endothelium and intracellular migrations of fibrillogranular material, thus potentially causing progressive vision loss.


Last updated on 30 April 2004