Effects of Relative Humidity and Ambient Temperature on the Ballistic Delivery of Micro-Particles to Excised Porcine Skin
2004; Elsevier BV; Volume: 122; Issue: 3 Linguagem: Inglês
10.1111/j.0022-202x.2004.22320.x
ISSN1523-1747
AutoresM. A. F. Kendall, Stephen Rishworth, Fiona Carter, Thomas J. Mitchell,
Tópico(s)Proteins in Food Systems
ResumoThe effectiveness of ballistic particle delivery to the skin is often dependent upon breaching the stratum corneum (SC) and targeting cells within defined layers of the viable epidermis. This paper experimentally determines the influence of relative humidity (RH) and temperature on the ballistic delivery of particles to the skin. Gold particles of radius 0.9±0.6 μm were accelerated by a hand-held supersonic device to impact freshly excised porcine skin at 410–665 m per s. Increasing the RH from 15% to 95% (temperature at 25°C) led to a particle penetration increase by a factor of 1.8. Temperature increases from 20°C to 40°C (RH at 15%) enhanced particle penetration 2-fold. In both cases, these increases were sufficient to move the target layer from the SC to the viable epidermis. Relative trends in particle penetration compared well with predictions from a theoretical model well. Calculated absolute penetration depths are 6-fold greater than the measurements. The inversely calculated dynamic yield stress of the SC is up to a factor of 10 higher than reported quasi-static measurements, due to changes in tissue failure modes over a strain-rate range spanning 10 orders of magnitude. If targeted particle delivery is required, it is recommended that the environmental RH and temperature be monitored. The effectiveness of ballistic particle delivery to the skin is often dependent upon breaching the stratum corneum (SC) and targeting cells within defined layers of the viable epidermis. This paper experimentally determines the influence of relative humidity (RH) and temperature on the ballistic delivery of particles to the skin. Gold particles of radius 0.9±0.6 μm were accelerated by a hand-held supersonic device to impact freshly excised porcine skin at 410–665 m per s. Increasing the RH from 15% to 95% (temperature at 25°C) led to a particle penetration increase by a factor of 1.8. Temperature increases from 20°C to 40°C (RH at 15%) enhanced particle penetration 2-fold. In both cases, these increases were sufficient to move the target layer from the SC to the viable epidermis. Relative trends in particle penetration compared well with predictions from a theoretical model well. Calculated absolute penetration depths are 6-fold greater than the measurements. The inversely calculated dynamic yield stress of the SC is up to a factor of 10 higher than reported quasi-static measurements, due to changes in tissue failure modes over a strain-rate range spanning 10 orders of magnitude. If targeted particle delivery is required, it is recommended that the environmental RH and temperature be monitored. relative humidity stratum corneum Epidermal powder injection (EPI) is a needle-free technique in which pharmaceutical agents, formulated as particles, are accelerated to sufficient momentum to penetrate the outer layer of the skin and achieve a pharmacological effect.Sanford et al., 1987Sanford J.C. Klein T.M. Wolfe E.D. Allen N. Delivery of substances into cells and tissues using a particle bombardment process.Part Sci Technol. 1987; 5: 27-37Crossref Scopus (274) Google Scholar initially pioneered this method with systems designed to deliver DNA-coated metal particles (radii ∼1 μm) with adapted guns into plant cells for genetic modification. The concept of the ballistic delivery of particles to tissue, known as biolistics, has been more recently extended to a range of research areas in plants, animal species (Loehr et al., 2000Loehr B.I. Wilson P. Babiuk L.A. van Drunen Littel-van den Hurk Gene gun-mediated DNA immunization primes development of mucosal immunity against bovine herpes virus 1 in cattle.J Virol. 2000; 74: 6077-6086Crossref PubMed Scopus (72) Google Scholar;Sudha et al., 2001Sudha P.M. Low S. Kwang J. Gong Z.Y. Multiple tissue transformation in adult Zebra fish by gene gun bombardment and muscular injection of naked DNA.Mar Biotechnol. 2001; 3: 119-125Crossref PubMed Scopus (34) Google Scholar;Yoshida et al., 2001Yoshida A. Nagata T. Uchijama M. Higashi T. Koide Y. Advantage of gene gun-mediated over intramuscular inoculation of plasmid DNA vaccine in reproducible induction of specific immune responses.Vaccine. 2001; 18: 1725-1729Crossref Scopus (94) Google Scholar), and in vitro test models (Smith et al., 2001Smith S.G. Poulam M.P. Selby P.J. Jackson A.M. 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In this application, gold particles (typically of 0.3–3 μm radius), coated with plasmid DNA coding for specific antigens, are delivered into the epidermis (Roy et al., 2000Roy M.J. Wu M.S. Barr L.J. et al.Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine.Vaccine. 2000; 19: 764-778Crossref PubMed Scopus (340) Google Scholar). Biolistic DNA vaccination allows the direct transfection of Langerhans cells as well as keratinocytes within the viable epidermis, hence allowing the antigen to be processed via the exogenous pathways and thereby generating a balanced immune response (Porgador et al., 1998Porgador A. Irvine K.R. Iwasaki A. Barber B.H. Restifo N.P. Germain R.N. Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization.J Exp Med. 1998; 188: 1075-1082Crossref PubMed Scopus (466) Google Scholar;Lesinski et al., 2001Lesinski G.B. Smithson S.L. Srivastava N. Chen D.X. Widera G. Westerink J. A DNA vaccine encoding a peptide mimic of Streptococcus pneumoniae serotype 4 capsular polysaccharide induces specific anti-carbohydrate antibodies in Balb/c mice.Vaccine. 2001; 19: 1717-1726Crossref PubMed Scopus (63) Google Scholar). The location of Langerhans cells as a biolistic target is tightly defined, with: •a vertical position at a consistent suprabasal location (Hoath and Leahy, 2002Hoath S.B. Leahy D.G. Formation and function of the stratum corneum.in: Marks R. Levenge J. Voegli R. The Essential Stratum Corneum. Martin Dunitz, London2002Crossref Google Scholar);•a spatial distribution in the horizontal plane evenly distributed throughout the skin (Numahara et al., 2001Numahara T. Tanemura M. Nakagawa T. Takaiwa T. Spatial data analysis by epidermal Langerhans cells reveals an elegant system.J Dermatol Sci. 2001; 25: 219-228Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar); and•a constitution of 2% of the total epidermal cell population (Bauer et al., 2001Bauer J. Bahmer F.A. Worl J. Neuhuber W. Schuler G. Fartasch M. A strikingly constant ratio exists between Langerhans cells and other epidermal cells in human skin. A stereologic study using the optical dissector method and the confocal laser scanning microscope.J Invest Dermatol. 2001; 116: 313-318Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar). In order to target cells at such tightly defined locations, an understanding of the mechanisms of epidermal ballistic particle delivery is required. To meet this goal, the velocity distribution of particles generated by early EPI systems was determined (Bellhouse et al., 1997Bellhouse B.J. Quinlan N.J. Ainsworth R.W. Needle-less delivery of drugs, in dry powder form, using shock waves and supersonic gas flow, Paper 9555, Proceedings of the 21st International Symposium on Shock Waves Great Keppel Island, Australia1997Google Scholar;Quinlan et al., 2001Quinlan N.J. Kendall M.A.F. Bellhouse B.J. Ainsworth R.W. Investigations of gas-particle flow in first generation dermal PowderJect needle-free drug delivery systems.Shock Waves. 2001; 10: 395-404Crossref Scopus (60) Google Scholar; Kendall et al 1Kendall MAF, Quinlan NJ, Thorpe SJ, Ainsworth RW, Bellhouse BJ: Measurements of the gas and particle flow within a converging–diverging nozzle for high speed powdered vaccine and drug delivery. Exp Fluids J accepted Dec 15, 2003), leading to improved EPI systems delivering particles to skin targets with uniform velocities over a range of discrete conditions (Kendall et al., 2003bKendall M.A.F. Mitchell T.M. Wrighton-Smith P. Intradermal ballistic delivery of micro-particles into excised human skin for drug and vaccine applications.J Biomech. 2003Google Scholar;Kendall, 2002Kendall M.A.F. The delivery of particulate vaccines and drugs to human skin with a practical, hand-held shock tube-based system.Shock Waves J. 2002; 12: 22-30Crossref Scopus (81) Google Scholar). These devices have been employed in excised human skin studies (Wrighton-Smith, 2001Wrighton-Smith P. Delivery of particles by powder injection. University of Oxford, 2001Google Scholar; Kendall et al 1Kendall MAF, Quinlan NJ, Thorpe SJ, Ainsworth RW, Bellhouse BJ: Measurements of the gas and particle flow within a converging–diverging nozzle for high speed powdered vaccine and drug delivery. Exp Fluids J accepted Dec 15, 20031Kendall MAF, Quinlan NJ, Thorpe SJ, Ainsworth RW, Bellhouse BJ: Measurements of the gas and particle flow within a converging–diverging nozzle for high speed powdered vaccine and drug delivery. Exp Fluids J accepted Dec 15, 2003), and porcine and canine buccal mucosa, ex vivo and in vivo biolistics experiments (Mitchell, 2003Mitchell T.M. The ballistics of micro-particles into the mucosa and skin. University of Oxford, 2003Google Scholar). In these particle impact studies, the mechanisms of particle impact were explored with a theoretical model, 2Based on a representation first proposed byDehn, 1987Dehn J. A unified theory of penetration.Int J Impact Eng. 1987; 5: 239-248Crossref Scopus (35) Google Scholar.2Based on a representation first proposed byDehn, 1987Dehn J. A unified theory of penetration.Int J Impact Eng. 1987; 5: 239-248Crossref Scopus (35) Google Scholar. which attributes the particle resistive force (D) to plastic deformation and target inertia D=12ρtAv2+3Aσy(1) where ρt and σy are the density and yield stress of the target, A is the particle cross-sectional area, and v is the particle velocity. The yield stress (sometimes known as the breaking stress) is the stress at which the tissue begins to exhibit plastic behavior. Using the assumptions ofMitchell et al., 2003Mitchell T.M. Kendall M.A.F. Bellhouse B.J. A ballistic study of micro-particle penetration to the oral mucosa.Int J Impact Eng. 2003; 28: 581-599Crossref Scopus (45) Google Scholar, (1) may be integrated to obtain the penetration depth as a function of particle impact and target parameters. Expression (1) shows that the yield stress and density of the stratum corneum (SC) and viable epidermis are important in the ballistic delivery of particles to the epidermis. The mechanical properties of the SC are strongly influenced by the water content of the tissue and hence the ambient humidity (Wildnauer et al., 1971Wildnauer R.H. Bothwell J.W. Douglas A.B. Stratum corneum properties I. Influence of relative humidity on normal and extracted stratum corneum.J Invest Dermatol. 1971; 56: 72-78Abstract Full Text PDF PubMed Scopus (144) Google Scholar;Christensen et al., 1977Christensen M.S. Hargens C.W. Nacht S. Gans E.H. Viscoelastic properties of intact human skin: Instrumentation, hydration effects and the contribution of the stratum corneum.J Invest Dermatol. 1977; 69: 282-286Abstract Full Text PDF PubMed Scopus (89) Google Scholar;Rawlings et al., 1995Rawlings A. Harding C. Watkinson A. Banks J. Ackerman O. Sabin R. The effect of glycerol and humidity on desmosome degradation in the stratum corneum.Arch Dermatol Res. 1995; 287: 457-464Crossref PubMed Scopus (191) Google Scholar;Dobrev, 1996Dobrev H. In vivo non-invasive study of the mechanical properties of the human skin after single application of topical corticosteroids.Folia Med (Plovdiv). 1996; 38: 7-11PubMed Google Scholar;Nicolopoulos et al., 1998Nicolopoulos C.S. Giannoudis P.V. Glaros K.D. Barbanel J.C. In vitro study of the failure of skin surface after influence of hydration and preconditioning.Arch Dermatol Res. 1998; 290: 638-640Crossref PubMed Scopus (17) Google Scholar). In tensile tests,Wildnauer et al., 1971Wildnauer R.H. Bothwell J.W. Douglas A.B. Stratum corneum properties I. Influence of relative humidity on normal and extracted stratum corneum.J Invest Dermatol. 1971; 56: 72-78Abstract Full Text PDF PubMed Scopus (144) Google Scholar determined the ultimate breaking strength of the excised human SC, conditioned by the variation in ambient relative humidity (RH). By applying the SC thickness versus RH measurements ofBlank et al., 1984Blank I.H. Maloney J. Emslie A.G. Simon I. Apt C. The diffusion of water across the stratum corneum as a function of its water content.J Invest Dermatol. 1984; 82: 188-194Abstract Full Text PDF PubMed Scopus (238) Google Scholar, the breaking strengths are converted into yield stresses: 22.5–3.2 MPa with increasing RH from 0% to 100%. The effect of ambient temperature on the properties of the SC has also been investigated (Papir et al., 1975Papir Y.S. Hsu K.-H. Wildnauer R.H. The mechanical properties of stratum corneum, I. The effect of water and ambient temperature on the tensile properties of newborn rat stratum corneum.Biochim Biophys Acta. 1975; 399: 170-180Crossref PubMed Scopus (85) Google Scholar;Alonso et al., 1995Alonso A. Nilce C.M. Tabak M. Effect of hydration upon the fluidity of intercellular membranes of stratum corneum: An EPR study.Biochim Biophys Acta. 1995; 1237: 6-15Crossref PubMed Scopus (58) Google Scholar). Increasing the SC temperature from 25°C to 60°C correspondingly decreased the breaking stress from 17 to 1.9 MPa (Papir et al., 1975Papir Y.S. Hsu K.-H. Wildnauer R.H. The mechanical properties of stratum corneum, I. The effect of water and ambient temperature on the tensile properties of newborn rat stratum corneum.Biochim Biophys Acta. 1975; 399: 170-180Crossref PubMed Scopus (85) Google Scholar). We have not found published measurements of the viable epidermis yield stress as a function of either RH or temperature. Considering the SC work ofWildnauer et al., 1971Wildnauer R.H. Bothwell J.W. Douglas A.B. Stratum corneum properties I. Influence of relative humidity on normal and extracted stratum corneum.J Invest Dermatol. 1971; 56: 72-78Abstract Full Text PDF PubMed Scopus (144) Google Scholar andPapir et al., 1975Papir Y.S. Hsu K.-H. Wildnauer R.H. The mechanical properties of stratum corneum, I. The effect of water and ambient temperature on the tensile properties of newborn rat stratum corneum.Biochim Biophys Acta. 1975; 399: 170-180Crossref PubMed Scopus (85) Google Scholar in the context of (1), there is a theoretical basis for a dependency of the deceleration force on an impacting particle on the ambient temperature and RH. In theory, this would lead to variations in the particle penetration depth, influencing the targeted particle delivery. The aim of this study is to determine experimentally the effect of temperature and humidity on the ballistic penetration of particles into the skin. This aim was met by experiments in which gold particles were fired into freshly excised porcine skin, maintained at environmental conditions over a range of temperature and humidity. The gold particles were delivered to the tissue by a hand-held, helium gas-powered biolistic delivery device. After injection into the skin, measurements of the final particle position were obtained from histological sections. The results were compared with calculations from the theoretical penetration model. The applicability of the SC material properties obtained from quasi-static measurements to the high-strain-rate ballistic particle injection was also investigated by comparisons with the experimental data and calculations with the unified penetration model. The collated penetration data from histology slides are plotted as a function of the RH in Figure 1a. Particle injection in an environment at 15% RH resulted in a penetration depth of 7.9±2.5 μm (mean±standard deviation) from a sample of 401 particles (n=401). Increases in RH led to deeper ballistic particle penetration. For example, the upper limit in RH of 95% resulted in a penetration depth of 22±8.9 μm from particle injection at 95% RH. This range in RH results in an increase in particle penetration depth by a factor of 1.8 (p<0.0005, Student's two-sided t test for two independent means with a 5% significance level). Also plotted in Figure 1a are the corresponding theoretical particle penetrations with RH using the unified penetration model and the bilayer approximation for the epidermis. The numerical values assigned to the calculated target parameters are listed in Table I.Table IParameters and assigned values used in the theoretical calculations of the particle penetration depth as a function of RHSkin regionParameterValueSourceStratum corneumσsc (MPa)22.5–3.2Wildnauer et al., 1971Wildnauer R.H. Bothwell J.W. Douglas A.B. Stratum corneum properties I. Influence of relative humidity on normal and extracted stratum corneum.J Invest Dermatol. 1971; 56: 72-78Abstract Full Text PDF PubMed Scopus (144) Google Scholar(0%–100% RH)ρsc (kg per m3)1500Duck, 1990Duck F.A. Physical Properties of Tissue: A Comprehensive Reference Book. Academic Press, London1990Google Scholartsc (μm)10–15.6Blank et al., 1984Blank I.H. Maloney J. Emslie A.G. Simon I. Apt C. The diffusion of water across the stratum corneum as a function of its water content.J Invest Dermatol. 1984; 82: 188-194Abstract Full Text PDF PubMed Scopus (238) Google Scholar and measurement(0%–93% RH)Viable epidermisσve (MPa)2.2Actin tensile,Kishino and Yanagida, 1988Kishino A. Yanagida T. Force measurements by micromanipulation of a single actin filament by glass needles.Nature. 1988; 334: 74-76Crossref PubMed Scopus (522) Google Scholar10Epithelium,Mitchell et al., 2003Mitchell T.M. Kendall M.A.F. Bellhouse B.J. A ballistic study of micro-particle penetration to the oral mucosa.Int J Impact Eng. 2003; 28: 581-599Crossref Scopus (45) Google Scholarρve (kg per m3)1150Duck, 1990Duck F.A. Physical Properties of Tissue: A Comprehensive Reference Book. Academic Press, London1990Google Scholar Open table in a new tab The assumptions for the numerical parameters listed in Table I are: (1)In the absence of published porcine data, the porcine SC yield stresses (σsc) are equivalent to breaking strength measurements on excised samples of SC from humans (Wildnauer et al., 1971Wildnauer R.H. Bothwell J.W. Douglas A.B. Stratum corneum properties I. Influence of relative humidity on normal and extracted stratum corneum.J Invest Dermatol. 1971; 56: 72-78Abstract Full Text PDF PubMed Scopus (144) Google Scholar). Porcine and human σsc values were assumed to be comparable because of similarities in morphology and functional characteristics between the species (Meyer et al., 1978Meyer W. Shwarz R. Neurand K. The skin of domestic mammals as a model for the human skin, with reference to the domestic pig.in: Simon G.A. Pasker Z. Klingberg M.A. Kaye E. Current Problems in Dermatology. Skin: Drug Application and Evaluation of Environmental Hazards. Vol. 7. Karger, New York1978: 39-52Google Scholar;Monteiro-Riviere, 1986Monteiro-Riviere N. Ultrastructural evaluation of porcine integument.in: Tumbleson M.E. Swine in Biomedical Research. Plenum Press, New York1986: 641-655Google Scholar;Adrega et al., 2001Adrega S. Kanikkannan N. Singh M. Comparison of the effect of fatty alcohols on the permeation of melatonin between porcine and human skin.J Control Rel. 2001; 77: 17-25Crossref PubMed Scopus (90) Google Scholar).(2)Breaking strength is converted into yield stress using the SC thickness (tsc) measurements. The SC thickness is dependent upon the RH. SC thicknesses are obtained by linear interpolation of the data reported byBlank et al., 1984Blank I.H. Maloney J. Emslie A.G. Simon I. Apt C. The diffusion of water across the stratum corneum as a function of its water content.J Invest Dermatol. 1984; 82: 188-194Abstract Full Text PDF PubMed Scopus (238) Google Scholar, which increase from 10 to 15.6 μm as RH ranged from 0% to 93% (shown in Figure 1a). This thickness range agrees with the values measured from histology slides in our study, such as in Figure 4.(3)The density of the SC (ρsc) and viable epidermis (ρve) are 1500 and 1150 kg per m3, respectively (Duck, 1990Duck F.A. Physical Properties of Tissue: A Comprehensive Reference Book. Academic Press, London1990Google Scholar).(4)No published data on the viable epidermis yield stress (σve) are directly applicable to the bilayer model. As an alternative, σve is estimated from the material properties of cells in the viable epidermis. Keratinocytes form the majority of viable epidermal cells. Within these cells, the cytoskeleton is important for structural integrity (Alberts et al., 2002Alberts B. Johnson A. Lewis J. Raff M. Roberts K. Walter P. Molecular Biology of the Cell. 4th edn. Garland Science, New York2002Google Scholar). Furthermore, actin fibers are present in the cytoskeleton at a high concentration. The yield stress of a single actin filament in quasi-static tension tests is 2.2 MPa (Kishino and Yanagida, 1988Kishino A. Yanagida T. Force measurements by micromanipulation of a single actin filament by glass needles.Nature. 1988; 334: 74-76Crossref PubMed Scopus (522) Google Scholar). In torsion, however, yield stresses of actin approach 7 MPa (Tsuda et al., 1996Tsuda Y. Yasutake H. Ishino A. Yanagida T. Torsional rigidity of single actin filaments and actin–actin bond breaking force under torsion measured directly by in vitro manipulation.Procs Natl Acad Sci USA. 1996; 93: 12937-12942Crossref PubMed Scopus (228) Google Scholar). Moreover,Janmey, 1991Janmey P.A. Mechanical properties of cytoskeletal polymers.Curr Opin Cell Biol. 1991; 2: 4-11Crossref Scopus (137) Google Scholar reports that different instruments in the measurement of F-actin rheology can result in differences in the viscoelastic properties of two orders of magnitude. Also, as shown in Figure 5a, the structure of viable epidermal cells varies considerably from the basal layer to the granular layer (Fuchs and Raghavan, 2002Fuchs E. Raghavan S. Getting under the skin of epidermal morphogenesis.Nature. 2002; 3: 199-209Google Scholar). This incomplete and variable description of the mechanical properties makes it difficult to construct and accurate representation of σve throughout the viable epidermis. For simplicity, we assume σve is a constant, using a lower and upper value in the calculations. As a lower bound, calculations are performed with σve set to 2.2 MPa, matching the tension yield stress of an actin fiber. As an upper bound, σve is 10 MPa, which is greater than the torsion yield of actin and is within the range of quasi-static SC yield stresses.Figure 5Schematic diagram of the structure of the epidermis of mammalian skin (a), and the corresponding bilayer approximation of the epidermis used for the theoretical penetration model (b). Penetration Case A denotes particle delivery into the stratum corneum (dsc), whereas in Case B the stratum corneum is fully breached (tsc) and the final particle location is within the viable epidermis (dve). The impact velocity is vi, while the input velocity for the viable epidermis is vi, ve.(adapted from Fuchs and Raghavan, 2002Fuchs E. Raghavan S. Getting under the skin of epidermal morphogenesis.Nature. 2002; 3: 199-209Google Scholar)View Large Image Figure ViewerDownload (PPT)(5)The unified penetration model is applicable to the ballistic delivery of particles to the epidermis. This assumption is supported by earlier work, in which calculations with the unified penetration model match particle penetration measurements with very good agreement (Kendall et al., 2003bKendall M.A.F. Mitchell T.M. Wrighton-Smith P. Intradermal ballistic delivery of micro-particles into excised human skin for drug and vaccine applications.J Biomech. 2003Google Scholar;Mitchell, 2003Mitchell T.M. The ballistics of micro-particles into the mucosa and skin. University of Oxford, 2003Google Scholar;Mitchell et al., 2003Mitchell T.M. Kendall M.A.F. Bellhouse B.J. A ballistic study of micro-particle penetration to the oral mucosa.Int J Impact Eng. 2003; 28: 581-599Crossref Scopus (45) Google Scholar). The epidermal yield stress in this earlier work, however, was determined semi-empirically to fit the measurements. These yield stress values were significantly higher than the reported quasi-static SC yield stresses. Calculations using these assumptions in Figure 1a show an increase in particle penetration with increasing RH; however, the theoretical and experimental depths are considerably different. For example, the calculated penetration depths are up to a factor of 3 or 6 greater (with assumptions of σve of 10 and 2.2 MPa, respectively) than the measured values at the corresponding RH. As expected, the calculated penetration depths are sensitive to our σve assumptions. In Figure 1b, the differences between the measured and theoretical particle penetration are explored by directly examining σsc. The measured quasi-static SC yield stresses used in the calculations (fromWildnauer et al., 1971Wildnauer R.H. Bothwell J.W. Douglas A.B. Stratum corneum properties I. Influence of relative humidity on normal and extracted stratum corneum.J Invest Dermatol. 1971; 56: 72-78Abstract Full Text PDF PubMed Scopus (144) Google Scholar) are plotted. Also shown in Figure 1b are the quasi-static σsc values required for the calculated ballistic penetration depths to match the measurements. There is a large difference between the quasi-static σsc and inversely calculated ballistic stresses which peak at 170 MPa. At a low RH, the ballistic-to-static difference in σsc is a factor of 7.5, decreasing to a factor of 3.5 at a higher RH. Furthermore, as the RH is increased, the calculated SC yield stress (σsc) becomes more sensitive to the viable epidermis (σve) approximations. This is expected, as the SC is not breached at the lower RH values. Figure 2a shows the particle penetration data from the ambient temperature experiments. The data were processed in the same way as the RH experiments. There is a significant increase in particle penetration (p<0.0005, Student's two-sided t test for two independent means with a 5% significance level) with an increase in the ambient temperature. For example, particle administration at a temperature of 20°C gave a penetration depth of 6.0±3.1 μm. Experiments at 40°C, however, produced a penetration depth of 18.2±8.0 μm (i.e., a factor of 2 increase). Also in Figure 2a are theoretical penetration depths from the unified penetration model using the following assumptions. Published porcine σsc values as a function of temperature were not found. Instead, the existing σsc values for neonatal rats (Papir et al., 1975Papir Y.S. Hsu K.-H. Wildnauer R.H. The mechanical properties of stratum corneum, I. The effect of water and ambient temperature on the tensile properties of newborn rat stratum corneum.Biochim Biophys Acta. 1975; 399: 170-180Crossref PubMed Scopus (85) Google Scholar) were used, with the assumption of similarity with porcine properties. This assumption is in part supported by "excellent agreement" (Papir et al., 1975Papir Y.S. Hsu K.-H. Wildnauer R.H. The mechanical properties of stratum corneum, I. The effect of water and ambient temperature on the tensile properties of newborn rat stratum corneum.Biochim Biophys Acta. 1975; 399: 170-180Crossref PubMed Scopus (85) Google Scholar) between neonatal rat and human SC material properties. In turn, it has been stated that the morphologies of the human and porcine SC are similar. The SC thickness (tsc) was set at 10.9 μm using the results fromBlank et al., 1984Blank I.H. Maloney J. Emslie A.G. Simon I. Apt C. The diffusion of water across the stratum corneum as a function of its water content.J Invest Dermatol. 1984; 82: 188-194Abstract Full Text PDF PubMed Scopus (238) Google Scholar at RH 15%. This agrees with our measurements of 10.6±1.3 μm (n=30). The other parameters in the calculations were assigned the values listed in Table I. With these assumptions, the calculated particle penetration depths are considerably greater than the measurements. This discrepancy is consistent with the RH results Figure 1a. In this case, however, the ambient temperature was varied. In Figure 2b, the differences between quasi-static (fromPapir et al., 1975Papir Y.S. Hsu K.-H. Wildnauer R.H. The mechanical properties of stratum corneum, I. The effect of water and ambient temperature on the tensile properties of newborn rat stratum corneum.Biochim Biophys Acta. 1975; 399: 170-180Crossref PubMed Scopus (85) Google Scholar) and ballistic yield stresses (calculated by the described method) are plotted as a function of the environmental temperature of the skin. Again, the relative effects of the RH results F
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