Penetration Routes Research Articles

Penetration Route of the Selective Glucocorticoid Receptor Agonist SA22465 and Betamethasone into Rabbit Meibomian Gland Based on Pharmacokinetics and Autoradiography

Meibomian glands are modified sebaceous glands embedded within specific types of dense connective tissues. This study investigated drug penetration into meibomian glands following a single topical administration in rabbits. We measured time course concentrations of the selective glucocorticoid receptor agonist (SEGRA) SA22465 and betamethasone in lid margins, palpebral conjunctival epithelium, and meibomian glands following a single instillation using a newly established collection method. We also visualized the distribution of 14C-SA22465 in eyelid tissue sections using microautoradiography. Concentrations of SA22465 and its major metabolite SA22313 were highest in lid margins, followed by palpebral conjunctival epithelium and meibomian glands in a 100-fold descending order. Betamethasone exhibited similar distribution profiles with smaller concentration differences. The distribution of silver grains as a quantitative index of radioactivity in eyes and eyelids was determined in a subjective manner using microautoradiographs, which revealed that the highest distribution of silver grains was associated with the cornea, followed by posterior segment tissues, such as the sclera, choroid, and retina. Low levels were associated with more internal ocular tissues and a greater number of compartments. Moderate levels of radioactivity were associated with meibomian glands and connective tissues, including the nictitating membrane. In contrast, meibomian ducts contained only background levels of radioactivity. Our findings indicate that the transconjunctiva is the most likely route of drug entry into meibomian glands following ocular administration rather than the central meibomian duct; however, this distribution is limited. A physiologic barrier may restrict drug penetration across the tarsal plate.

The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

Background: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu’s cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. Methods: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC0–t, AUMC0–t), area under the zero and first moment curves from 0 to infinity (AUC0–∞, AUMC0–∞), maximum plasma concentration (Cmax) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. Results: In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with the control group, the indomethacin skin percutaneous rate of the FCT low-intensity group (FCTL) was 35.52%, and the enhancement ratio (ER) at 9 h was 1.76X, roughly equivalent to the penetration enhancing effect of the CPEs and iontophoresis. Secondly, the indomethacin percutaneous ratio of the FCT middle-intensity group (FCTM) and FCT high-intensity group (FCTH) were 47.36% and 54.58%, respectively, while the ERs at 9 h were 3.58X and 8.39X, respectively. Thirdly, pharmacokinetic data showed that in vivo indomethacin percutaneous absorption of the FCT was much higher than that of the control, that of the FCTM was slightly higher than that of the CPE, and that of the FCTM group was significantly higher than all others. Meanwhile, variance analysis indicated that the combination of the FCT penetration enhancement method and the CPE method had beneficial effects in enhancing skin penetration: the significance level of the CPE method was 0.0004, which was lower than 0.001, meaning the difference was markedly significant; the significance level of the FCT was also below 0.0001 and its difference markedly significant. The significance level of factor interaction A × B was lower than 0.0001, indicating that the difference in synergism was markedly significant. Moreover, SEM and TEM images showed that the SC surfaces of Sprague-Dawley rats treated with FCT were damaged, and it was difficult to observe the complete surface structure, with SC pores growing larger and its special “brick structure” becoming looser. This indicated that the barrier function of the skin was broken, thus revealing a potentially major route of skin penetration. Conclusion: FCT, as a new form of transdermal penetration technology, has significant penetration effects with TCM characteristics and is of high clinical value. It is worth promoting its development.

Inhalation - Route of EDC exposure in seabirds (Larus argentatus) from the Southern Baltic

Despite the presence of endocrine disrupting mercury, PAHs, alkylphenols and bisphenol A in inhaled air, scientific literature lacks information on their penetration into the lungs. Large lung capacity in birds makes this route of penetration more significant than in other animals.The studies were conducted on lungs of herring gulls found in the Gulf of Gdansk area. The results were juxtaposed with other tissues, including the intestines, which reflect the main, alimentary penetration route of harmful substances into the organism. It was determined that the capacity of bird's lungs, affects the efficiency with which mercury is absorbed from the air. Birds found to have high mercury concentrations in lungs had low PAHs concentrations, what was determined by the fact that the birds foraged in two different areas, as well as on different trophic levels. The alimentary route of phenol derivatives into the organism was of greater significance than inhalation.

Skin penetration-inducing gelatin methacryloyl nanogels for transdermal macromolecule delivery

In this study, the suitability of gelatin methacryloyl (GelMA) nanogels for transdermal delivery of macromolecules was demonstrated. The synthesis of GelMA nanogels (GNs) and fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) loaded GelMA nanogels (FGNs) were implemented when confined in water-in-oil nanoemulsion droplets via the photopolymerization of the methacryloyl substituents to create crosslinked nanogels. Both GNs and FGNs existed as fine particles in aqueous condition (pH 7.4) for 7 days. No distinct aggregation of nanogel particles were observed. In the MTT assay, high percentage of cell viability indicated that GNs did not exhibit any growth inhibitory effect or significant cytotoxicity. The skin penetration study results showed that FGNs permeated across the epidermis and into the dermis of a porcine model when compared to the FITC-BSA dissolved in PBS. Possible penetration routes of FITC-BSA through the stratum corneum (SC) were illustrated by visualizing the SC structure with fluorescent signals of FITC-BSA. The penetration mechanism of FGNs across the SC layer was successfully demonstrated by explaining three penetration routes (intercellular, follicular, and transcellular route). The results suggest that GNs have a potential as a transdermal delivery carrier for hydrophilic macromolecules.

Exposure to minimally processed pear and melon during shelf life could modify the pathogenic potential of Listeria monocytogenes

Survival and virulence of foodborne pathogens can be influenced by environmental factors such as the intrinsic properties of food as well as the extrinsic properties that contribute to food shelf life (e.g., temperature and gas atmosphere). The direct contribution of food matrix characteristics on the survival of L. monocytogenes during fresh-cut fruit shelf life is not very well understood. In addition, the gastrointestinal tract is the primary route of listeriosis infection and penetration of the intestinal epithelial cell barrier is the first step in the infection process. Hence, the pathogenic potential of L. monocytogenes, measured as the capability for the organism to survive a simulated gastrointestinal tract and the proportion of cells able to subsequently adhere to and invade differentiated Caco-2 cells, subjected to fresh-cut pear and melon shelf life, was investigated. Samples were inoculated, stored at 10 °C for 7 days and evaluated after inoculation and again after 2 and 7 days of storage. A decrease in L. monocytogenes’ capacity to survive a simulated gastrointestinal tract was observed with increasing storage time, regardless of the fruit matrix evaluated. Furthermore, L. monocytogenes placed on fresh-cut pear and melon was subjected to an attachment and invasion assay after crossing the simulated gastrointestinal tract. After inoculation, pathogen on fresh-cut pear showed 5-fold more capacity to adhere to Caco-2 cells than pathogen on fresh-cut melon. After 2 days of storage, L. monocytogenes grown on fresh-cut melon showed similar adhesive capacity (1.11%) than cells grown on pear (1.83%), but cells grown on melon had the higher invasive capacity (0.0093%). We can conclude that minimally processed melon could represent a more important hazard than pear under the studied shelf life.

O Centro-Oeste brasileiro e suas transformações econômicas de 1970 a 2012

O Centro-Oeste é a região brasileira que compreende o Brasil Central. É a segunda região brasileira menos povoada. Sua vegetação é predominantemente composta pelo ecossistema Cerrado. A região é detentora de importante reserva de água doce e concentra as nascentes de rios pertencentes às principais bacias hidrográficas da América do Sul. Politicamente, o Centro-Oeste é a sede das decisões político-administrativas do país, por abrigar o Distrito Federal. Após o declínio da mineração, a região se converteu à exploração da pecuária e da agricultura extensivas. Recentemente, tem se tornado a grande produtora de grãos do Brasil e sede de várias agroindústrias. Esse período de maiores transformações na região iniciou-se pelo avanço da economia cafeeira paulista. A sua ocupação econômica deu-lhe condição específica na divisão territorial do trabalho, como produtora de alimentos e matérias primas para populações e indústrias do Sudeste. Esse processo é discutido no presente artigo. Ao final aportam-se informações obtidas em pesquisa de campo e realiza análise geral do processo de evolução demográfica da região estudada, particularizando os seus três estados.Código JEL | J43; O18; Q13.

How to Create an Embryo Penetration Route.

Numerous past investigations into human implantation have tended to pay attention to the mechanism of embryo adhesion to endometrial cells or embryo invasion into endometrial stromal tissue. For successful pregnancy, however, embryo penetration through the endometrial epithelial cell (EEC) sheet is also absolutely required. To improve the performance of assisted reproductive technology, implantation studies should also focus on EEC dynamics, in particular, the action of EECs during embryo penetration. Although only EEC apoptosis has been proposed as a mechanism for the formation of the embryo penetration route, we have also recently reported that characteristic EEC collective motion, regulated by the epithelial to mesenchymal transition, also plays a key role in permitting embryo penetration. We review here how EECs form embryo penetration routes in light of our findings.

Historical Overview of the Laboratory Measurements of Moisture Dependent Thermal Conductivity and the Integration of these Measurement Results into the Design of Hungarian Building Structures

The thermal conductivity of installed building materials can differ from the declared value, which is determined under specific laboratory conditions given in standards (Fülöp, 2007; MSZ EN ISO 10456, 2008). In this article, the author investigates moisture as a thermal conductivity modifying effect and the design of building structures in relation to this effect. In the first chapter, the international and Hungarian results of laboratory measurements of the value of moisture dependent thermal conductivity factors are summarized. In the next section, the application of these results in the design of Hungarian building structures is discussed, especially with regard to the flat roof, due to its increased exposure. With the framework of a historical overview, the most important flat roof layer combinations are described from the perspective of how thermal insulation material was protected against the different routes of moisture penetration. Concluding the article, a terrace restoration (a building constructed in the early 1900s originally without separate thermal insulation material) of Dr Zsuzsanna Fülöp is described to illustrate the points referred above.

Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB).

BackgroundThe blood brain barrier (BBB) controls the brain microenvironment and limits penetration of the central nervous system (CNS) by chemicals, thus creating an obstacle to many medical imaging and treatment procedures. Research efforts to identify viable routes of BBB penetration have focused on structures such as micelles, polymeric nanoparticles and liposomes as drug carriers, however, many of them failed to provide unequivocal proof of BBB penetration. Here we proved that gold nanoparticles (AuNPs) penetrate the BBB in rats to reach brain regions.ResultsInjection of AuNPs to the abdominal cavity of rats resulted in levels of gold found in blood, urine, brain regions and body organs. After perfusion the concentration of gold in brain regions diminished dramatically indicating that most of the gold was in venous blood and not in the brain tissues. Injection of Na, K or Ca ion channel blockers reduced BBB penetration by half. A biological half-life of 12.9 ± 4.9 h was found for the gold nanoparticles. Possible mechanisms for the transport of AuNPs through the BBB are discussed.ConclusionsBBB penetration by AuNPs is spontaneous without the application of an external field. A major amount of gold resides in blood vessels therefore perfusion required. Ion channel blockers can be used to control the transport of AuNPs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0133-1) contains supplementary material, which is available to authorized users.

Application of Nano- and Micro-Particles on the Topical Therapy of Skin-Related Immune Disorders

Several immune disorders may occur in the skin, such as psoriasis, atopic dermatitis and vitiligo. As the largest organ in the human body, skin provides a unique and non-invasive platform to deliver active pharmaceutical ingredients into superficial lesions or even circulations. In recent years, novel pharmaceutical particles were applied in the topical treatment for skin-related immune disorders to keep the stability, improve the bioactivity, as well as reduce the toxicity of APIs, or even provide a targeting property for the agents. As the pathogenesis of these diseases is increasingly highlighted, the target site and function of topical delivery of particles become more clear and specific. Therefore, diversified surface engineering of vehicles has gradually gained more attention. Appropriate size, charge and surface modification of API-loaded particles can bring out a favorable effect for skin disorders. In this review, comparison of normal and pathological skin structure, penetration route of various drug particles, nano- and micro- particles applied for skin-related immune disorders are summarized. In-vitro and in-vivo evaluation methods for topical therapy of immune disorders will be discussed. Moreover, recent applications of particles loaded with active ingredients from herbal medicines or biological agents for skin immune disorders are also highlighted.

Cream formulation impact on topical administration of engineered colloidal nanoparticles.

In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

Reversible Storage of Lithium in Three-Dimensional Macroporous Germanium

Germanium (Ge) has received much attention when compared to other alloy anode materials like silicon [1, 2], due to its still high enough theoretical capacity of 1,600 mAh g-1 (4.4 Li+ ions per Ge atom), good lithium ion diffusivity (more than 400 times higher than in silicon at room temperature: 1.41 × 10-14 cm2 s-1 for Si and 6.51 × 10-12 cm2 s-1 for Ge), high electronic conductivity (104 times higher than silicon)[3] and a lower specific volume change during the lithium insertion/extraction process [4]. Nevertheless, the, compared to silicon, tin or other lithium storage metals, high price of germanium is the major drawback for the commercialization of this anode material.[5] Furthermore, as with silicon, tin and their derivatives [6, 7] severe particle pulverization can be triggered by a large volume change during the lithium alloying (to form LixGe) and de-alloying processes (to reform Ge), which results in electronically disconnected germanium particles as well as a continuous reactivity of the anode with the electrolyte. As a result, the electrode suffers from a rapid capacity fading upon cycling. Many approaches have been pursued to accommodate the volume changes of germanium, such as preparation of Ge/carbon composites[8], fabrication of Ge-based alloy composites (Sn22/Ge78/Carbon)[9] and designing a special morphology of germanium (e.g. nanoparticles[10], nanotubes[11] and nanowires[12]). In recent years, more attention has been paid to these anode materials to avoid the common problems of ultra-fine powders (especially those with a particle size of less than 100 nm), such as a strong aggregation tendency, which results in increased lithium ion diffusion pathways, their difficulty to handle and an enhanced binder requirement leading to a lower energy density. The basic strategy is that a porous structure can offer sufficient local void space to absorb the volume expansion of alloys like silicon, tin or germanium and thereby to improve the cycling stability. In order to buffer the large volume changes during lithiation/de-lithiation and offer an easier electrolyte penetration route, the concept of this work is to create the active material with a macro-porous structure. Moreover, the open structure of the porous particles is favorable for fast transport of Li+and gives rise to a high charge/discharge rate performance. In this work, we report a facile synthesis route, i.e. a simple heat treatment procedure, for the formation of three-dimensional porous germanium particles by a magnesiothermic reduction method (2Mg + GeO2 → 2MgO + Ge). The synthesized GeO2 which shows a hexagonal-like morphology with an average particle size of about 700 nm, as shown in the SEM and TEM images in Figure 1a and b, respectively, serves not only as the template, but also as the germanium source in the magnesium reduction procedure. XRD characterization illustrates that it is feasible to obtain germanium via a magnesium reduction reaction between Mg and GeO2. Three-dimensional porous germanium particles, which basically retain the original morphology of GeO2 (Figure 1c and d), can be obtained by this synthesis route. The porous germanium electrode displays a stable reversible capacity of 1,131 mAh g-1 for 200 cycles at 1C and a high rate capability of up to 5C. This great improvement can be attributed to the optimized nanostructure related to the uniformly distributed pores and very thin pore walls in the range of 30 nm. Figure 1. a) SEM and b) TEM images of GeO2; c) and d) SEM images of porous germanium.

Effect of Cross-Linking Density of Silicone Encapsulant on Sulfur Compound Gas Permeability of Light-Emitting Diode

To study the effect of cross-linking density of silicone encapsulant on gas permeability, a light-emitting diode (LED) package was produced with two kinds of silicone, methyl-group (silicone A) and phenyl-group (silicone B), and a sulfur compound gas permeability test of the fabricated packages was performed. We found that the main penetration route of sulfur compound gas into the Ag-plated layer in an LED package could be directly observed by inserting Ag wire in an encapsulant. The persistency rate of radiant flux increased as the curing time of the silicone encapsulant became longer. When electron beam is irradiated on an LED package, the persistency of radiant flux is also increased.

Effects of silver nanoparticles on human health

AbstractThere has been a great deal of attention and research devoted on nanoparticels (NPs) over the last 10 years. From current knowledge in the field of nanotoxicology, it has become evident that the most NPs, if not all are more toxic than bulk materials. The rapid progress and developing has been leading to concerns about the potential risk associated with the use and application of NPs on human health and the environment. Silver nanoparticles (SNPs) are one of the most available and commercially distributed nanomaterials around the world. In order to understand how human health can be affected by SNPs, quantification and detection of SNPs in biological systems have to be conducted in different models. It seems that respiratory and gastrointestinal systems as well as the skin are the major routes of SNPs penetration into the body. Research on SNPs toxicity is mostly conducted in vitro, and the available human and animal data are relatively limited. This review attempts to focus on the characterization and quantification of the potential harmful effects of SNPs on human health.

Insights to the ethiopathogenesis of human nail diseases

The finger nails or ungues are hard covering which form the horny zone of the epidermis. They overlie the dorsal aspect of the distal phalanges. Nail diseases are distinct from diseases of the skin. Although nails are a skin appendage, they have their own signs and symptoms which may relate to other medical conditions. The nail disease has clinical signs which reflect patho biologic changes of the nail plate and nail matrix. There are a number of conditions that can affect our nails, with different causes and treatments. Common causes of fingernail problems include injury, infection and skin diseases such as eczema and psoriasis. Topical therapy is highly desirable because of its non-invasiveness, ability to target drugs to the site of action, minimizing systemic adverse effects and improving patient compliance. Continuous exposal of nail to warm, moist environments usually develops nail infection. Nail plate is main route for penetration of drug. Varity of conventional formulation like gel, cream and also oral antifungal are available for treatment of nail infection. The major problem associated with conventional nail treatment for nail disorders is to deliver the active therapeutically. However possible means to enhance nail penetration must be explored in greater depth before effective local treatments for fungal nail infections are developed.

Significant Promotion to Electrical Properties of Sm Modified BaLa<I><SUB>x</SUB></I>Sm<I><SUB>x</SUB></I>TiO<SUB>3</SUB> (0.001 ≤ <I>x</I> ≤ 0.005) Powders: A Novel Precursor Gaseous Penetration Route

Significant Promotion to Electrical Properties of Sm Modified BaLa<I><SUB>x</SUB></I>Sm<I><SUB>x</SUB></I>TiO<SUB>3</SUB> (0.001 ≤ <I>x</I> ≤ 0.005) Powders: A Novel Precursor Gaseous Penetration Route

Investigation of the mechanism of enhanced skin penetration by ultradeformable liposomes.

This study aimed to determine the mechanism by which ultradeformable liposomes (ULs) with terpenes enhance skin penetration for transdermal drug delivery of fluorescein sodium, using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Skin treated with ULs containing d-limonene, obtained from in vitro skin penetration studies, was examined via TEM to investigate the effect of ULs on ultrastructural changes of the skin, and to evaluate the mechanism by which ULs enhance skin penetration. The receiver medium collected was analyzed by TEM and CLSM to evaluate the mechanism of the drug carrier system. Our findings revealed that ULs could enhance penetration by denaturing intracellular keratin, degrading corneodesmosomes, and disrupting the intercellular lipid arrangement in the stratum corneum. As inferred from the presence of intact vesicles in the receiver medium, ULs are also able to act as a drug carrier system. CLSM images showed that intact vesicles of ULs might penetrate the skin via a transappendageal pathway, potentially a major route of skin penetration.

Assessment of cracks in reinforced concrete by means of electrical resistance and image analysis

The durability of cracked reinforced concrete is a serious concern in the construction industry. Cracks represent fast routes for chloride penetration, which can result in reinforcement corrosion. Bending or tapered cracks have the characteristic of being wider at the surface and becoming narrower towards the reinforcement. In reinforced concrete, secondary cracks can be found at the concrete steel interface. Their influence on concrete durability remains uncertain. Electrical resistance and resistivity have been commonly related to transport properties of concrete. This paper studies bending cracks in reinforced concrete specimens by measuring the electrical resistance across the crack. Cut sections of the specimens were subsequently impregnated and photographed. Image analysis tools were employed for determining the crack dimensions. It was found that the relative increase in electrical resistance and the crack volume were related to the crack opening displacement (COD) at the concrete surface.

An oil spill surveillance program for Lake Pontchartrain

This article describes an oil spill surveillance strategy implemented in response to BP's 2010 MC252 oil well blowout in the Gulf of Mexico. A three-pronged strategy consisted of Geographic Information System (GIS) monitoring of the surface slick, hydrodynamic modeling of the potential movement of the slick within the Basin, and weekly field reconnaissance. Our analysis was completed in near real time during the event and the results and predictions helped local responders minimize oiling impacts in Lake Pontchartrain. No prior planning was undertaken before this crisis response, and this article reports our support activities as they happened. For the GIS component, a remote sensing derived surface slick outline layer was obtained to produce near daily maps showing the slick's proximity to Lake Pontchartrain along with weather conditions and deployed response assets. This regular monitoring of the slicks' location was complemented by hydrodynamic numerical modeling that simulated the currents that determined the trajectories of oil particles. These data were ground-truthed through weekly reconnaissance trips that assessed the potential routes of oil penetration into Lake Pontchartrain for the presence of sheen, tarballs, and other oil constituents. Despite the ad hoc design and on-the-fly implementation, these three assessments provided consistent and actionable information.

The presence and distribution of bacteria in dentinal tubules of root filled teeth

To investigate the distribution of bacteria within the dentine tubular network in a two-chamber model in order to determine a possible route of penetration. Root canals of teeth in the experimental group (n = 16) were instrumented and root filled using AH26 and gutta-percha. Canals in the teeth serving as positive (n = 1) and negative (n = 1) controls were instrumented, but not root filled. A two-chamber model was fabricated for each root - upper chambers were inoculated weekly with Streptococcus gordonii in brain-heart infusion broth over 90 days. Turbidity of the lower chamber was checked daily. Samples that showed turbidity during the experimental period and samples that showed no signs of turbidity at 90 days were fractured and prepared for SEM examination. SEM examination for the presence of bacteria within the dentinal tubules was performed in the cervical, middle and apical root thirds. In each root third, the depth of bacterial penetration was recorded as inner, middle or outer dentine. Bacteria were most commonly detected in the cervical third (14 of 30 areas). Irrespective of the root third examined, bacteria were most commonly detected in the inner dentine (i.e. adjacent to the root canal). Only two samples demonstrated bacterial penetration in the outer dentine. The dentine tubular network provides a potential pathway for bacteria to penetrate tooth roots in a two-chamber model.