Remedies for Oral Mucosal Diseases

Fig. 12.1

Healing of aphthous ulcers on the upper labial mucosa following 2 days of treatment with locally applied doxycycline gel (see Ref. 8). The gel was applied to the ulcer four times per day for 2–3 days. Patients recorded the presence of ulcers, taste, discomfort and altered sensation daily in a diary

Fig. 12.2

Results of the clinical trial for the doxycycline gel treatment of aphthous ulcers (see Ref. 8). 70% of ulcers had healed by the third treatment day in the test group but only in 25% of subjects receiving the placebo (p < 0.005). The hydrogel was well accepted and reduced discomfort, even in the placebo group

Fig. 12.3

The stabilities achieved in developed doxycycline formulations (Patlolla et al. unpublished data). The highest stability is achieved in an aqueous based formulation at 4 °C that was 100% stable even after >4 years, whereas the stability of doxycycline is only for few days when in contact with water molecules. At 25 °C the aqueous formulation was 100% stable for 1 month, whereas stability is only for a few days when doxycycline solution is left at room temperature. Even at 25 °C the precomplexed doxycycline containing microparticle-loaded buccal films was found to be 75–80% stable after 7.5 months whereas no trace of doxycycline was seen in only doxycycline containing films. The formation of degradation product 4-epidoxycycline was completely prevented in precomplexed microencapsulated doxycycline microparticles at 4, 24 ad 40 °C after 7.5 months

12.3.2 Topical Preparations Containing Monocaprin

Another area of interest to this research collaboration was the development of topical preparations of monocaprin, an antimicrobial monoglyceride that was known to be effective against enveloped viruses, particularly herpes simplex virus, and also to hinder growth of Candida albicans (Thorgeirsdóttir et al. [2024]). Monocaprin (Fig. 12.4) is a natural breakdown product of triglycerides that are commonly found in plant oils, particularly coconut oil. It is classified as “Generally Regarded As Safe (GRAS)” by the US Food and Drug Administration. This product is quite different from commonly used antimicrobial compounds and, therefore, was unlikely to promote drug resistance to such microorganisms if it became widely used for treating clinical conditions. The activity of monocaprin against herpes simplex virus was tested in a topical preparation that also included doxycycline. Consequently, the research team were combining the antiviral activity together with the inhibition of matrix metalloproteinase by doxycycline in a treatment for cold sores (secondary herpes infections; Fig. 12.5). The activity of these two pharmaceutical compounds was to eliminate the virus and to reduce inflammation so that the lesions would heal more quickly. A placebo-controlled clinical trial of these compounds showed the combined topical drug therapy to be significantly more efficient at reducing the time of clinical signs of aphthous ulcers and pain from the lesions (Skulason et al. [25]).

Fig. 12.4

Monocaprin : a monoglyceride that has been found to kill enveloped viruses and various bacteria, both Gram-negative and Gram-positive, and the yeast Candida spp. (see Refs. 20, 23)

Fig. 12.5

Clinical appearance of a cold sore (“herpes labialis ”). Treatment with topical application of a gel containing monocaprin and doxycycline shortened the time to complete the healing of cold sores both at the prodromal stage of the cold sore or after vesicles have first appeared. The treatment time was reduced by 2 days for both stages of the cold sore (p < 0.05) (see Ref. 25)

Further studies of antimicrobial activity of monocaprin were aimed at evaluating its anti-candidal effect. While oral infections with Candida albicans can have numerous underlying causes, it is most commonly seen as an infection of the oral mucosa associated with patients wearing dentures (Figs. 12.6 and 12.7). This group of patients is increasingly elderly and do not have good denture hygiene. There may also be associated conditions and therapeutic products in these patients that promote denture stomatitis. As denture stomatitis has a considerable effect on the quality of life of this patient group, the research team thought that developing anti-candidal monocaprin products could be potentially highly beneficial. Consequently, monocaprin was incorporated into a denture adhesive material and also into a hydrogel, and these compounds were tested in clinical trials to measure the reduction of the counts of yeasts from standardized samples, the reduction of mucosal inflammation and the patients’ opinions on the treatment outcomes [2628]. The clinical trial was carried out in a residence for geriatric patients. Initial sampling from the fitting surfaces of dentures, palatal and lingual mucosa, was carried out using sterile sponges that were moistened in sterile water and placed on the sampling surface and then transferred to Sabouraud agar plates for the culture of Candida. The study showed that 60% of subjects had dense growth of Candida (> 50 cfu/cm 2 ) from the denture and palatal samples. A double-blind placebo-controlled trial of a denture adhesive and hydrogel containing 3% monocaprin was then carried out among these patients over a 4-week period. Patients receiving the adhesive or gel that contained monocaprin had a rapid decline in the counts of Candida to <10 cfu/cm2. No problematic side effects were noted by patients, but an improved function of their dentures was reported by several patients that received the monocaprin-containing products [26, 28]. This study, and an earlier study by this group evaluating the anti-candidal activity of monocaprin, found the beneficial effect of reducing counts of Candida to be short-lived, and the yeast counts began to rise again only a few days after the clinical trial had stopped. This reflects the environment under dentures, particularly in elderly patients, that will encourage the growth of Candida. Consequently a product containing monocaprin needs to be developed that is suitable for long-term use on the fitting surface of dentures especially for patients for whom denture cleaning is a problem.

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Aug 25, 2019 | Posted by in General Dentistry | Comments Off on Remedies for Oral Mucosal Diseases
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