Bernadette K. Drummond

The oral cavity as a site for systemic drug delivery

Abstract Currently there is a high level of interest in the use of the oral cavity as a portal for drug entry to the systemic circulation. As a site for drug delivery the oral cavity offers advantages over the conventional gastrointestinal route and the parenteral and other alternative routes of drug administration. It provides direct entry into the systemic circulation thereby avoiding the hepatic first pass effect, ease of administration and the ability to terminate delivery when required. In addition the membranes that line the oral cavity are readily accessible and exhibit robustness and fast cellular recovery following local stress or damage. The oral cavity appears therefore to be a potential site for the delivery of drugs to the systemic circulation. However, this site is associated with limitations that restrict its use as a route for the systemic delivery of drugs. The low permeability of the membranes that line the oral cavity results in a low flux of drug; there appears to be the need to develop strategies which enhance drug penetration to improve bioavailability. The environment of the oral cavity and the continual secretion and swallowing of saliva are unique problems which need to be considered pre-formulation to ensure successful delivery of a drug via this route. This review highlights the advantages of systemically delivering drugs via the oral mucosa and discusses the membrane, drug, dosage form and environmental issues which limit its use as a site for systemic drug delivery.

Mineral density of hypomineralised enamel

OBJECTIVES To characterize molar-incisor hypomineralisation (MIH) defects of different severities quantitatively and qualitatively using X-ray microtomography (XMT) and to measure the range of reduction in mineral density (MD) of MIH enamel compared with the normal range. METHODS Ten sound teeth and ten MIH teeth were scanned using a commercial XMT system. Four hydroxyapatite phantoms of different densities were used as calibration standards with each scan. A calibration equation derived from the phantoms with each tooth was used for MD calibration. MD was traced from the cementum-enamel junction (CEJ) to the cusp tip and from the dentine-enamel junction (DEJ) to the outer enamel surface. RESULTS In sound teeth, MD increased from CEJ to cusp/incisal tip, while in MIH teeth MD dropped from the CEJ to the occlusal region, then increased again at the cusp tip. MD was highest midway between DEJ and outer enamel in sound teeth. In MIH, enamel showed normal thickness and MD was highest near the DEJ and then decreased towards the outer enamel. MD of MIH enamel was on average about 19% lower than sound enamel. The MIH defects seemed to follow the incremental lines of enamel formation. CONCLUSIONS MIH defects are hypomineralised defects of different severities that follow the natural incremental lines of enamel formation. Cuspal areas are usually only mildly affected and cervical enamel always appears to be sound.

Protein content of molar-incisor hypomineralisation enamel

OBJECTIVES The aim of the study was to compare the relative amounts and nature of the proteinous content of sound and molar-incisor hypomineralisation (MIH) enamel. METHODS TCA (20%) was used to dissolve the mineral phase and precipitate the proteins from enamel pieces sectioned from sound and MIH enamel. The protein content was estimated using a miniaturized version of the method of Lowry et al. Samples of the solubilised protein were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), stained with Coomassie Blue R250 and tryptic fingerprint/mass spectrometry (MS/MS) of bands in excised gel pieces used for protein identification. RESULTS Compared to sound enamel, brown enamel showed a 15-21-fold higher protein content, and yellow and chalky enamel showed about 8-fold higher protein content. Tryptic fingerprint/MS performed on excised 50-70kDa areas demonstrated serum albumin, type I collagen and antitrypsin to be common to all types of enamel. Yellow and brown enamel showed more abundant serum albumin and antitrypsin, and the presence of serum antithrombin. Albumin is reported to be an inhibitor of crystal growth, and antitrypsin and antithrombin inhibit kallikrein 4 proteolytic activity. CONCLUSIONS The combination of the effects of serum proteins on developing enamel may result in elevated proteinous content and reduced mineral content as seen in MIH enamel.

Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial

The prevalence of dental caries continues to increase, and novel strategies to reverse this trend appear necessary. The probiotic Streptococcus salivarius strain M18 offers the potential to confer oral health benefits as it produces bacteriocins targeting the important cariogenic species Streptococcus mutans, as well as the enzymes dextranase and urease, which could help reduce dental plaque accumulation and acidification, respectively. In a randomized double-blind, placebo-controlled study of 100 dental caries-active children, treatment with M18 was administered for 3 months and the participants were assessed for changes to their plaque score and gingival and soft-tissue health and to their salivary levels of S. salivarius, S. mutans, lactobacilli, β-haemolytic streptococci and Candida species. At treatment end, the plaque scores were significantly (P = 0.05) lower for children in the M18-treated group, especially in subjects having high initial plaque scores. The absence of any significant adverse events supported the safety of the probiotic treatment. Cell-culture analyses of sequential saliva samples showed no differences between the probiotic and placebo groups in counts of the specifically enumerated oral micro-organisms, with the exception of the subgroup of the M18-treated children who appeared to have been colonized most effectively with M18. This subgroup exhibited reduced S. mutans counts, indicating that the anti-caries activity of M18 probiotic treatments may be enhanced if the efficiency of colonization is increased. It was concluded that S. salivarius M18 can provide oral health benefits when taken regularly.

Relationship between laser fluorescence and enamel hypomineralisation

OBJECTIVES To study the relation between the mechanical properties of hypomineralised enamel, and its laser fluorescence (LF). METHODS Five extracted teeth with molar-incisor hypomineralisation (MIH) were sectioned longitudinally through the defects and polished to prepare the hypomineralised enamel for testing. Hardness (H) and elastic modulus (E) of enamel were measured using nanoindentation. Measurement recording started from the cervicoenamel junction and proceeded occlusally in increments of 200 microm. Laser fluorescence readings were taken along the same line and at the same sites using a DIAGNOdent pen. RESULTS H, E, and LF readings from cervical enamel were within the expected range for normal sound enamel. After log transformation of the H and E measurements to allow for linear correlation analysis, there was a significant and moderately strong inverse correlation between LF and H or E samples (r (between specimens)=0.59, r (between specimens)=0.39, respectively; p<0.001). CONCLUSIONS This study shows that, in the absence of dental caries, increased DIAGNOdent readings can indicate enamel hypomineralisation. While the increased LF readings in carious enamel are thought to be related to the presence of caries bacterial metabolites, the increased readings in hypomineralised enamel may be related to proteins in the hypomineralised enamel and/or light scattering by the inhomogeneous enamel.

Orofacial and dental trauma of young children in Dunedin, New Zealand

AIM  The aims were to identify the predominant causes and types of orofacial injury in young children attending clinics at a University Dental School in Dunedin, New Zealand. MATERIAL AND METHODS  A retrospective analysis of data from the records of all children aged 0-10years who had been seen for orofacial trauma in 1999 and 2000 was undertaken. RESULTS AND CONCLUSIONS Three hundred traumatic incidents in 288 children were analysed; 86.6% had causes noted. In very young children, most injuries were because of falls, while collisions, falling and sports were responsible for more injuries in school-aged children. Playground equipment and ride-on vehicles played a role particularly in the older children. There were no incidents of trauma as a result of road traffic accidents. Ten injuries were caused by animals, mainly dogs. Location was recorded for two-thirds of accidents: the predominant place was at home, followed by school. No seasonal variation was apparent. There were 228 non-dental injuries, of which the majority were to the lips. The predominant dental injuries in both dentitions were concussions and subluxations with a significantly higher occurrence of both in the primary dentition (P<0.001). Upper central incisors were most often involved. The age distribution for boys and girls was similar. In conclusion, the causes and types of orofacial trauma in this group of young New Zealand school children attending a university dental school were similar to other studies, except for the high proportion of concussions recorded in both dentitions. While the injuries were well described, not all records noted the cause or location. This has resulted in changes to the standard recording form to provide consistency in data capture. Information from this study will also be used to support child injury prevention strategies in New Zealand.

Zoledronic acid and geranylgeraniol regulate cellular behaviour and angiogenic gene expression in human gingival fibroblasts.

The mevalonate pathway (MVP) and the anti-angiogenic effect of bisphosphonates have been shown to play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the MVP by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon-alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co-addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3/7 was detected in zoledronic-acid-treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid-like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (P < 0.05, FR > ± 2) up-regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon-alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic-acid-treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.

Raman spectroscopic characterisation of resin-infiltrated hypomineralised enamel

Raman spectroscopy was used to investigate how the effect of pre-treatment protocols, with combinations of hydrochloric acid (HCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H2O2), for molar–incisor hypo-mineralisation (MIH) altered the penetration depth of polymer infiltrants (ICON, DMG, Hamburg, Germany). Furthermore, the effect on the structure of the MIH portions of the teeth with treatment is examined using multivariate analysis of spectra. It was found that pre-treatment protocols improved penetration depths. The structure of the MIH portion post-treatment appeared much closer to that of normal enamel suggesting a diminution of protein in the MIH region with treatment.

Influence of dental care on children's oral health and wellbeing.

Background Dental problems in early childhood can have a very significant effect not only on the oral health of young children but on their quality of life and that of their families. Added to this are the long term risks they carry into the permanent dentition.Aim To review current literature on the management of early childhood caries and its influence on wider oral and general health.Results Recent studies suggest that the risks for dental caries, periodontal disease, malocclusion and other general health problems including overweight and obesity may be increased in children who have had early childhood caries. Traditional restoration of damaged primary teeth has been shown to have only moderate outcomes depending on the techniques and materials used and the ability of children to cooperate because of age or other factors.Conclusions More recent interesting approaches that seal enamel caries, only partially remove carious dentine or attempt to entirely seal carious dentine lesions merit not only discussion but also longer term investigation. With increasing demands on health funding, dentistry must look at how the most appropriate care can be provided to allow children to reach adulthood with healthy permanent dentitions – something that less than half the population currently achieve.

Avulsion and replantation of a primary incisor tooth

Avulsion of a primary tooth is a serious dental trauma, and the guidelines of the International Association of Dental Traumatology and textbooks in paediatric dentistry do not recommend replantation. Such management can result in severe damage to the supporting structures, and together with avulsion itself is commonly associated with developmental disturbances of the permanent tooth. We report the case of replantation in a 9-month-old child with a successful outcome, in a unique situation where conditions were optimal and careful long-term follow up was possible.