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Introduction, aim: Extraesophageal reflux (EER) is the backflow of gastric fluids (most often acidic) above the level of the upper esophageal sphincter (it differs from gastroesophageal reflux). The symptoms of extraesophageal reflux are non-specific, of varying intensity and depend on the location of the pathological action of the refluxate. In the case of the effect of refluxate on the hard dental tissue, EER can contribute to the formation of dental erosions. In addition to refluxate, other factors such as the composition of saliva and the microbiome of the oral cavity are discussed. In recent years, there has been a significant shift in the understanding of extraesophageal reflux, especially the pathogenesis, and the resulting implications for diagnosis and treatment. The aim of the article is to inform about EER and give an overview of the current possibilities of diagnosis and its treatment, as well as to summarize the results of recent meta-analyses regarding the role of EER in the development of dental diseases.Methods: The basis for the presented article was professional publications obtained in the PubMed, Cochrane Library and Scopus databases from 2002 to 2022. Publications were searched using a combination of keywords in English and Czech languages: extraesophageal reflux, gastroesophageal reflux, dental erosion. A total of 21 studies discussing the association between reflux and dental erosions were analyzed through review, clinical prospective and retrospective studies and meta analyses. The included studies were conducted in the adult population and information on gastroesophageal reflux in relation to the occurrence of dental erosions was used only if it was diagnosed by multichannel intraluminal pH impedance monitoring. The first part of the article presents a current view of the pathophysiology, diagnosis and treatment of EER. The second part summarizes knowledge about dental erosions. In the third part, studies dealing with the effect of EER on dental erosion are presented.Results: The obtained information indicates a higher prevalence of dental erosions in patients with EER compared to the healthy population. The reason is that acids of both exogenous and endogenous origins play an important role in dissolving enamel minerals, which ultimately leads to tooth erosion. Based on the analyzed studies, the relationship between reflux and the development of dental erosions cannot currently be considered causal, mainly due to the low quality of the studies. The authors recommend that further studies investigating the relationship between EER and dental damage should be conducted.Conclusions: Based on the findings, it can be assumed that extraesophageal reflux is involved in the development of dental diseases. A possible link is also supported by the fact that the prevalence of dental erosions in population with reflux or the prevalence of reflux in the population with dental erosions is much higher compared to the healthy population. In the future, however, further studies are needed to investigate the causality of extraesophageal reflux in the occurrence of dental erosions.

Lip tumors represent common type of neoplasia on the head and neck region. Squamous cell carcinoma of the lower lip is the most frequent tumor. It usually appears in elderly but recently it becomes more frequent in younger age groups. The prognosis is quite good, namely due to early diagnosis as the tumor is visible and the patients are seeking medical care. Early recognition and referral to specialist is necessary. This article reviews the recent literature and brings author´s experience and practical recommendation in the treatment of this disease. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) of the head and neck originates from the mucosal lining of the upper aerodigestive tract, including the lip, tongue, nasopharynx, oropharynx, larynx and hypopharynx. In this review, we summarise what is currently known about the potential function of primary cilia in the pathogenesis of this disease. As primary cilia represent a key cellular structure for signal transduction and are related to cell proliferation, an understanding of their role in carcinogenesis is necessary for the design of new treatment approaches. Here, we introduce cilia-related signalling in head and neck squamous cell carcinoma (HNSCC) and its possible association with HNSCC tumorigenesis. From this point of view, PDGF, EGF, Wnt and Hh signalling are discussed as all these pathways were found to be dysregulated in HNSCC. Moreover, we review the clinical potential of small molecules affecting primary cilia signalling to target squamous cell carcinoma of the head and neck area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Putnová, Putnová, Hurník, Štembírek, Buchtová and Kolísková.)

Introduction: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment., Methods: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression., Results: Among a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1 IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1 IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates., Discussion: The early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1 IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy., Trial Registration: The study is registered with Clinicaltrials.gov. - NCT05941676., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Blažek, Petráš, Hurník, Matoušek, Knybel, Čermáková, Štembírek, Cvek and Soumarová.)

Objective: Oral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC., Methods: We performed hierarchical clustering of principal components to identify distinct patterns of tumor growth and their association with patient prognosis. We also used next-generation sequencing to analyze somatic mutations in tumor and marginal tissue samples., Results: Our analyses uncovered that the grade of worst pattern of invasion (WPOI) is strongly associated with depth of invasion and patient survival in multivariable analysis. Mutations were primarily detected in the DNA isolated from tumors, but several mutations were also identified in marginal tissue. In total, we uncovered 29 mutated genes, mainly tumor suppressor genes involved in DNA repair including BRCA genes; however none of these mutations significantly correlated with a higher chance of relapse in our medium-size cohort. Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes., Conclusion: Even histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hurník, Režnarová, Chyra, Motyka, Putnová, Čermáková, Blažek, Fománek, Gaykalova, Buchtová, Ševčíková and Štembírek.)

Background: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis., Case Presentation: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet., Conclusions: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway., Objective: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival., Method: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined., Results: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year ( p = 0.083), 5-year ( p = 0.159), and overall survival ( p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year ( p = 0.083) and 5-year ( p = 0.159) survival., Conclusion: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Background: Eagle's syndrome (ES) is a term describing a group of symptoms associated with the elongation of the styloid process (SP) of the temporal bone or with ossification of the stylohyoid ligament. Clinically, it manifests through pain in the orofacial and pharyngeal regions, similar to that experienced by patients with temporomandibular joint disease. The presented paper aims to assess the evaluation of the success of surgical treatment and the complications associated with such treatment., Methods: Our retrospective study includes nine patients with ES treated in our Department Oral and Maxillofacial Surgery in years 2019-2023 (median age of 47 years) - all patients affected with this disease out of 2,716 patients examined at our department due to a temporomandibular joint disease. Eight of these patients underwent a surgical resection of the SP. The success and complications in these patients are evaluated in this study., Results: In seven patients, the problems disappeared or at least diminished, which is consistent with data from the literature. Postoperative complications such as deficit of the marginal branch of the facial nerve (n. VII), limited sticking the tongue out (n. XII), and velopharyngeal insufficiency (n. IX) occurred in three patients., Conclusion: The wide spectrum of clinical manifestations makes ES a condition that should be considered in the differential diagnosis of temporomandibular joint disorders, post-traumatic conditions, or complicated eruption of wisdom teeth or their extraction. ES can be treated conservatively or (mostly) surgically. Surgical treatment can be relatively successful and effective, but it is necessary to respect the anatomical placement of the SP, which can be associated with the development of complications, especially in cases with extremely long SP.

Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell carcinoma (HNSCC) is determined by the degree of invasiveness of the primary tumor and by the extent of metastatic spread into regional and distant lymph nodes. Moreover, the level of the perineural invasion itself associates with tumor localization, invasion's extent, and the presence of nodal metastases. Here, we summarize the current knowledge about different aspects of epigenetic changes, which can be associated with HNSCC while focusing on perineural invasion (PNI). We review epigenetic modifications of the genes involved in the PNI process in HNSCC from the omics perspective and specific epigenetic modifications in OSCC or other neurotropic cancers associated with perineural invasion. Moreover, we summarize DNA methylation status of tumor-suppressor genes, methylation and demethylation enzymes and histone post-translational modifications associated with PNI. The influence of other epigenetic factors on the HNSCC incidence and perineural invasion such as tobacco, alcohol and oral microbiome is overviewed and HPV infection is discussed as an epigenetic factor associated with OSCC and related perineural invasion. Understanding epigenetic regulations of axon growth that lead to tumorous spread or uncovering the molecular control of axon interaction with cancer tissue can help to discover new therapeutic targets for these tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hurník, Chyra, Ševčíková, Štembírek, Trtková, Gaykalova, Buchtová and Hrubá.)

Purpose: We evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer., Methods: Thirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70-72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables-tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4., Results: After a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%)., Conclusion: The combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

Background: Chronic wounds and their problematic healing is a widely discussed topic in all branches of medicine. In recent years, vacuum therapy appears to be a very successful non-invasive method supporting the healing of these wounds. The aim of this paper is to demonstrate the possibility of utilizing a vacuum system in the orofacial area where other conservative and surgical procedures have failed., Cases: The case reports demonstrate the use of vacuum therapy in non-healing postoperative wounds in cancer patients., Conclusion: Vacuum therapy has limited use in the orofacial area, but based on our experience, we can conclude that it has a very positive effect on the healing of chronic wounds. Thanks to this treatment, it was possible to reduce the frequency of dressings and significantly shorten the length of hospital stay. Despite these advantages, however, it is necessary to adhere to the conditions for the application of vacuum treatment.

The temporomandibular joint (TMJ) is a condylar synovial joint that, together with the masticatory muscles, controls mandibular movement during mastication. The rabbit is often used as a model species for studying the mechanisms of TMJ diseases, and in regenerative research. However, there are significant differences between rabbit and human TMJs that should be taken into account before using this model for experimental research. Here, we use several analytical approaches (radiography, computed tomography and magnetic resonance imaging) to enable a detailed description and analysis of the rabbit TMJ morphology. Moreover, possible surgical approaches have been introduced with a focus on available access into the rabbit TMJ cavity, which relate our findings to clinical usage.

Background: Buccal flexible films in the form of solid, thin, mucoadhesive patches can be used as dressings separating aphthous lesions from the environment of the oral cavity, which can in turn shorten the treatment period and reduce the pain perception., Methods: The clinical study was performed on 36 volunteers suffering from aphthous lesions. The first group was treated using standard means-by application of an oral gel containing cholin salicylate (Mundisal) on the aphthous lesion. The second group was treated with the same preparation; however, the lesion was covered with a mucoadhesive film following the application of the gel. The criteria for statistical evaluation were the size of lesions in relation to the length of the treatment and the subjective perception of the treatment results., Results and Conclusions: The application of buccal films covering aphthous lesions during the treatment significantly increased the rate of healing when compared with the standard methods of treatment. While the pain improvement was statistically significant as soon as Day 3 in the experimental group, it was only apparent on Day 5 in the control group, and the number of successfully treated patients (pain perception improving to visual analogue scale 2 or less) was at all time points higher in the experimental group than in the control group. The results imply that the use of buccal films for treatment of aphthous lesions is very promising and can lead to a significant reduction in the duration of patients' discomfort., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Frizzled 6 (FZD6) belongs to a family of proteins that serve as receptors in the WNT signaling pathway. FZD6 plays an important role in the establishment of planar cell polarity in many embryonic processes such as convergent extension during gastrulation, neural tube closure, or hair patterning. Based on its role during hair development, we hypothesized that FZD6 may have similar expression pattern and function in the dental lamina, which is also a distinct epithelial protrusion growing characteristically angled into the mesenchyme. Diphyodont minipig was selected as a model species because its dentition closely resemble human ones with successional generation of teeth initiated from the dental lamina. We revealed asymmetrical expression of FZD6 in the dental lamina of early as well as late stages during its regression with stronger expression located on the labial side of the dental lamina. During lamina regression, FZD6-positive cells were found in its superficial part and the signal coincided with the upregulation of molecules involved in epithelial-mesenchymal transition and increased migratory potential of epithelial cells. FZD6-expression was also turned on during differentiation of cells producing hard tissues, in which mature odontoblasts, ameloblasts, or surrounding osteoblasts were FZD6-positive. On the other hand, the tip of successional lamina and its lingual part, in which progenitor cells are located, exhibited FZD6-negativity. In conclusion, asymmetrical expression of FZD6 correlates with the growth directionality and side-specific morphological differences in the dental lamina of diphyodont species. Based on observed expression pattern, we propose that the dental lamina is other epithelial tissue, where planar cell polarity signaling is involved during its asymmetrical growth.

Chameleon teeth develop as individual structures at a distance from the developing jaw bone during the pre-hatching period and also partially during the post-hatching period. However, in the adult, all teeth are fused together and tightly attached to the jaw bone by mineralized attachment tissue to form one functional unit. Tooth to bone as well as tooth to tooth attachments are so firm that if injury to the oral cavity occurs, several neighbouring teeth and pieces of jaw can be broken off. We analysed age-related changes in chameleon acrodont dentition, where ankylosis represents a physiological condition, whereas in mammals, ankylosis only occurs in a pathological context. The changes in hard-tissue morphology and mineral composition leading to this fusion were analysed. For this purpose, the lower jaws of chameleons were investigated using X-ray micro-computed tomography, laser-induced breakdown spectroscopy and microprobe analysis. For a long time, the dental pulp cavity remained connected with neighbouring teeth and also to the underlying bone marrow cavity. Then, a progressive filling of the dental pulp cavity by a mineralized matrix occurred, and a complex network of non-mineralized channels remained. The size of these unmineralized channels progressively decreased until they completely disappeared, and the dental pulp cavity was filled by a mineralized matrix over time. Moreover, the distribution of calcium, phosphorus and magnesium showed distinct patterns in the different regions of the tooth-bone interface, with a significant progression of mineralization in dentin as well as in the supporting bone. In conclusion, tooth-bone fusion in chameleons results from an enhanced production of mineralized tissue during post-hatching development. Uncovering the developmental processes underlying these outcomes and performing comparative studies is necessary to better understand physiological ankylosis; for that purpose, the chameleon can serve as a useful model species., (© 2016 Anatomical Society.)

Due to its similarity to humans, the pig has proven to be a suitable biomodel for both research purposes and for training medical professionals, particularly in surgical specializations. For example, new implant materials have been tested on pig jaws and pigs have also been used in the development of new surgical techniques. For optimizing the effectiveness of such research or training, detailed data on the anatomy of their particular features are needed. At present, however, only limited information related to surgical and imaging anatomy of the facial and orbital areas of the pig and its comparison to human structures from the experimental surgery point of view is available in the literature. The aim of this study was to obtain such data and to compare the morphological structures of the porcine and human orbital regions and to lay down the foundation for practical use in experimental surgery. Ten pig heads were examined using computed tomography (CT) and magnetic resonance imaging (MRI) and, subsequently, a dissection of the orbit was carried out. Attention was focused on the structure of the orbit (floor, rim and nerves) frequently affected by pathological processes in humans (such as trauma, infection or tumours) and which consequently are frequently the subject of maxillofacial surgery. The porcine orbit is suitable for use in experimental medicine. However, if used in experiments, its anatomical peculiarities must be taken into consideration. Our study presents a foundation of basic knowledge for researchers who plan to use the pig as a biomedical model to investigate alternative treatments in the head region., (© The Author(s) 2015.)

Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge. This formulation consists of a mucoadhesive oral film with incorporated nanocomposite biomaterial that is able to release the drug directly at the target area. This study describes the unique approach of preparing mucoadhesive oral films from carmellose with incorporating a nanotechnologically modified clay mineral intercalated with chlorhexidine. The multivariate data analysis was employed to evaluate the influence of the formulation and process variables on the properties of the medical preparation. This evaluation was complemented by testing the antimicrobial and antimycotic activity of prepared films with the aim of finding the most suitable composition for clinical application. Generally, the best results were obtained with sample containing 20 mg of chlorhexidine diacetate carried by vermiculite, with carmellose in the form of nonwoven textile in its structure. In addition to its promising physicomechanical, chemical, and mucoadhesive properties, the formulation inhibited the growth of Staphylococcus and Candida; the effect was prolonged for tens of hours.

Mucoadhesive films represent the most developed medical form of buccal application. Despite the intense focus on buccal film-based systems, there are no standardized methods for their evaluation, which limits the possibility of comparison of obtained data and evaluation of the significance of influence of formulation and process variables on properties of resulting films. The used principal component analysis, together with a partial least squares regression provided a unique insight into the effects of in vitro parameters of mucoadhesive buccal films on their in vivo properties and into interdependencies among the studied variables. In the present study eight various mucoadhesive buccal films based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared using a solvent casting method or a method of impregnation, respectively. An ethylcellulose or hydrophobic blend of white beeswax and white petrolatum were used as a backing layer. The addition of polyethylene oxide prolonged the in vivo film residence time (from 53.24±5.38-74.18±5.13 min to 71.05±3.15-98.12±1.75 min), and even more when combined with an ethylcellulose backing layer (98.12±1.75 min) and also improved the film's appearance. Tested non-woven textile shortened the in vivo film residence time (from 74.18±5.13-98.12±1.75 min to 53.24±5.38-81.00±8.47 min) and generally worsened the film's appearance. Mucoadhesive buccal films with a hydrophobic backing layer were associated with increased frequency of adverse effects., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The pig represents a useful, large experimental model for biomedical research. Recently, it has been used in different areas of biomedical research. The aim of this study was to review the basic anatomical structures of the head region in the pig in relation to their use in current research. Attention was focused on the areas that are frequently affected by pathological processes in humans: the oral cavity with teeth, salivary gland, orbit, nasal cavity and paranasal sinuses, maxilla, mandible and temporomandibular joint. Not all of the structures have an equal morphology in the pig and human, and these morphological dissimilarities must be taken into account before choosing the pig as an experimental model for regenerative medicine.

The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers. The developed system combines pH-, time- and biodegradable polymer-based mechanisms for drug targeting to the colon. Pellet cores containing caffeine as model drug and chitosan and microcrystalline cellulose as excipients were prepared by the extrusion/spheronization method. The prepared pellets were film coated with a pH-dependent polymer, Eudragit FS 30 D. The coating total weight gain was 28.83% (w/w). Thanks to the application of an outer enteric film and the multiple unit design of the dosage form, the variability in gastric emptying was overcome, and a colon-specific targeting relied on the reproducibility of a small intestinal transit time, which was reported to be 3 ± 1 hours. A biodegradable polymer in the pellet core, chitosan, ensured the site-specific release of the model drug due to its solubility at the lower pH of the colonic region and by its biodegradability from the bacteria present. The efficiency of the system was confirmed by the in vivo testing of human saliva. The time of the first appearance of caffeine into the saliva, T(lag), was used as a parameter to estimate the disintegration time of the pellets into the gastrointestinal tract. The caffeine appeared in the saliva within 6.95 ± 1.12 hours (T(lag)) in 9 volunteers. A comparison of the reported colon arrival times indicates that the developed system is applicable to colonic drug delivery., (© 2012 Informa Healthcare USA, Inc.)