Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity.

COMPARATIVE ASSESSMENT OF SALINE VERSUS OCTENIDINE DIHYDROCHLORIDE DRESSING IN DIABETIC FOOT ULCERS

Diabetic foot ulcers are a common presenting complaint in many institutions catering to rural populations. The reasons for this can be the undiagnosed diabetes and lack of knowledge regarding complications. Care of diabetic foot ulcers involves systemic as well as local interventions. Among the local care methods is regular dressings using a good antimicrobial agent. Here Octenidine Dihydrochloride has shown promise. The present study was done to assess the efcacy of Octenidine Dihydrochloride in diabetic foot ulcers. The study used a pool of 80 subjects divided in two equal groups who were randomly subjected to saline and Octenidine Dihydrochloride dressings. The study observed that the mean rate of healing and wound coverage was signicantly better in Octenidine treated subjects when compared to saline group. Octenidine Dihydrochloride is a better topical agent when compared to saline in the present population sample.

The Effect of Incorporating Different Concentrations of Octenidine Dihydrochloride on the Degree of Conversion of an Experimental Flowable Resin Composite

BACKGROUND: One of the important parameters in assessing the definitive physical, mechanical, and biological characteristics of resin composites is the degree of conversion (DC), as composite qualities have been proven to improve with increasing the DC after photo-polymerization. Besides, fracture or secondary caries are the most common causes of composite resin failure. Accordingly, this reflects the need of formulating dental restorative materials possessing antibacterial activity. AIM: This study was designed to incorporate different concentrations of a new antibacterial agent (Octenidine dihydrochloride [OCT]) into an experimentally formulated flowable resin composite and evaluate its DC. MATERIALS AND METHODS: Four groups were tested in this study; group I was used as the control group, it’s a commercially available flowable composite “Herculite Ultra Flowable”. Group II was an experimental flowable composite with no antibacterial agent. During the preparation of the experimental flowable resin composite material, OCT antibacterial agent was added to the filler in special dark containers at a concentration of 1% wt. and 1.5% wt. respectively, in groups III and IV. The DC was measured and compared to the commercially available resin composite using the Fourier Transform Infrared spectroscopy method. RESULTS: Results of the current study showed that the mean values of DC ranged between (70.37 and 48.7), where Group1 showed the highest mean value, followed by Group 2 than Group 3, Group 4 specimens had the lowest mean value. The data showed that there is a statistically significant difference between all the tested groups. However, the DC was still within the accepted ranges for dental use. CONCLUSION: Based on the results obtained within the experimental conditions of this study it may be stated that the inclusion of the antibacterial OCT 1% and 1.5% wt., into the flowable resin composite showed satisfactory results for the DC as it met the ADA requirements for clinical use.

Impact of human wound exudate on the bactericidal efficacy of antiseptic products in quantitative suspension according to the European standard (DIN EN 13727)

By default, antimicrobial efficacy of antiseptics used in wound management is tested in vitro under standardized conditions according to DIN EN 13727, with albumin and sheep erythrocytes used as organic challenge. However, it is not clear whether these testing conditions do adequately reflect the wound bed environment. Therefore, the aim of this study was to compare the efficacy of different antiseptic products based on octenidine dihydrochloride (OCT), polyhexamethylene biguanide (PHX), and povidone-iodine under challenge with human wound exudate instead of standardized organic load in an in vitro setting according to DIN EN 13727. Bactericidal efficacy of the tested products was reduced to different extend when challenged with human wound exudate compared to standardized conditions. Overall, OCT-based products showed the necessary germ count reductions at the shortest exposure times (e.g., 15 seconds for octenisept®). PHX-based products were the least efficient. In addition to the protein content, other components of wound exudates, such as the microflora, seem to influence the efficacy of antiseptics. This study demonstrates that standardized in vitro test conditions only partly reflect actual wound bed conditions. Consequences for an amendment of existing test methods adapting organic load requirements and the feasibility of standardization of wound exudates are to be discussed.

Quality of life and therapeutic regimen management in onychomycosis patients and in vitro study of antiseptic solutions

Onychomycosis or tinea unguium (EE12.1) and Onychomycosis due to non-dermatophyte moulds (1F2D.5) (OM) is a fungal infection of the nail plates with a high prevalence that often affects vulnerable people with co-existing health problems. Gold standard pharmacological treatments for onychomycosis have been associated with low success rates and increasing antifungal resistance, suggesting that treatment outcome is dependent on multiple variables. Here, the prevalence of OM and quality of life were characterized in two vulnerable populations—Hospital patients and Homeless people. Comparing both groups, the most prevalent fungal species were identified in Hospital patients. Then, the in vitro fungicidal properties of the antiseptics povidone-iodine, polyhexamethylene biguanide-betaine, octenidine dihydrochloride, and a super-oxidized solution against two ATCC strains (Candida albicans and Aspergillus niger) and three clinical fungal isolates from Hospital patients (Candida parapsilosis, Trichophyton interdigitale, and Trichophyton rubrum) were tested. OM prevalence was high in both patient groups studied, who also reported a reduction in quality of life and concerns about the state of their feet. In addition, Hospital patients had a non-negligent therapeutic regimen management style. Antiseptics tested in vitro revealed antifungal properties. As antiseptics are low-cost and easy to apply and have few iatrogenic effects, the demonstration of fungicidal properties of these solutions suggests that they may constitute potential supportive therapeutics for OM.

3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications

Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept®, OCT) possess accurate printability and shape fidelity. This study also provides the protocol of ink’s use for the 3D printing of hydrogel scaffolds. The hydrogel’s physicochemical properties and drug release profiles from the hydrogel specimens to the external solution have been determined at two temperatures (20 and 37 °C). The release test showed a sustained OCT delivery into ultrapure water and the PBS solution. The temperature-responsive hydrogel exhibited antimicrobial activity against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa and demonstrated non-cytotoxicity towards fibroblasts. The thermoresponsive behavior along with biocompatibility, antimicrobial activity, and controlled drug release make this hydrogel a promising class of materials for wound dressing applications.

Effectiveness of local application of antiseptic with octenidin dihydrochloride molecule in smoking women with ASC-US and LSIL

This article presents the results of our own experience of topical use of the Prodexin antiseptic that is contained an octenidine dihydrochloride molecule as a monotherapy for ASC-US and LSIL cervical pathology (identified with in fluid cytology) associated with human papillomavirus in smoking women.Study objective: To study the efficacy of topical application of the octenidine dihydrochloride molecule in the Prodexin vaginal suppositories in the treatment of smoking women with ASC-US and LSIL.Materials and methods. The study involved 45 female smokers with identified ASC-US or LSIL. The complex of examination included: Pap test based on liquid cytology, testing for human papillomavirus 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 types in a quantitative format, screening for the causes of vaginitis, extended colposcopy to exclude cervical intraepithelial neoplasia II+. Prodexin suppositories were used according to a 3-month treatment regimen (20 suppositories daily, and then 10 suppositories in two consecutive cycles).Results. Clinical and laboratory assessment of the therapy effectiveness has convincingly shown its positive effect on the vagina and cervix. Treatment with the Prodexin antiseptic associated with microbiota normalization, colposcopic picture improvement and changes in the Pap smear to NILM I or II. Regress to NILM was recorded in 20 (86.9%) patients with ASC-US and in 15 (68.8%) women with LSIL.Conclusions. Prodexin allows to avoid a worsening of the situation and prevent the changes progression in HSIL. Proposed treatment had no side effects, was convenient to use and did not require additional visits to doctor during therapy. The control over the human papillomavirus and study of the viral load has been postponed for 6–12 months from the beginning of the examination, that will be the second stage of work.

Antibacterial Effects of Octenidine Dihydrochloride, and Benzalkanium Chloride on Acinetobacter Baumannii Strains Isolated from Clinical Samples and Determination of Genetic Diversity of Isolates by RAPD-PCR Method

Due to the emergence of antibiotic resistance in Acinetobacter baumannii which is one of the important causes of nosocomial infections, many problems have been raised in the successful treatment of patients with the subsequent mortality. So, the present study was performed to evaluate the antibacterial effect of Actinidine dehydrochloride, Actinisept, and Benzalkanium chloride against Acinetobacter baumannii strains isolated from clinical samples and to determine the genetic diversity of strains by RAPD-PCR. A total of 119 non-duplicate, suspected Acinetobacter baumannii isolates were collected and confirmed by conventional culture and biochemical tests and PCR technique. Susceptibility of the isolates to antibiotics was evaluated by standard Antibiotic susceptibility testing (AST). For antiseptics Octenidine dihydrochloride (OCT), Actinisept, and Benzalkonium chloride (BZK), Minimal inhibitory concentration (MIC) was assessed. The prevalence of Qac E and Qac delta E genes related to antiseptics was estimated by PCR. Finally, genetic diversity of strains was determined by RAPD-PCR. All 119 suspected isolates were confirmed as Acinetobacter baumannii using conventional tests and PCR. The isolates were mostly originated from blood samples. In AST, the lowest resistance was seen for ciprofloxacin and gentamicin. The MIC values were reported as OCT (15.26 µg) and BZK (640 µg). The antiseptic genes of qacE and qac ΔE1 were found to be present in 56 (47.05%) and 59 (49.57%) of isolates respectively. RAPD typing method revealed great diversity among A. baumannii isolates, with 37 clusters in isolates from ICU, of which 32 isolates were single and 5 were multiple. In conclusion, considering the increase of resistance to antiseptics, it is of importance to monitor the susceptibility of A. baumannii to antiseptics and to promote antiseptic stewardship in hospitals. Furthermore, in this study great diversity among A. baumannii was observed making it difficult to properly carry out infection control policies. analysis of RAPD-PCR typing results, and we found 37 clusters, among them 32 isolates were single and 5 were multiple. So, the method generated 37 RAPD type which shows great diversity among 57 out of 62 A. baumannii isolates at 80% cutoff.

Antimicrobial Efficacy of Octenidine Dihydrochloride and Artemisia Annua Plant Extract as Root Canal Irrigants – An In Vivo Study

Objectives: The study aimed to evaluate and compare the antimicrobial efficacy of two root canal irrigantsOctenidine dihydrochloride and herbal Artemisia annua plant extract. Methods: Forty-two maxillary central incisors teeth were selected which were divided into four groups – group A (Octenidine dihydrochloride with saline), group B (only Octenidine dihydrochloride), group C (Artemisia annua with saline), group D (only Artemisia annua). Samples for microbiological culturing were collected after access preparation, after biomechanical preparation, and after final irrigation in each group with the help of paper points. CFU count was observed for both aerobic and anaerobic bacteria. The results were collected and subjected to a Student t-test. Results: After statistical analysis, it was observed that bacterial reduction was seen in all the groups but the maximum reduction was observed in group A. Conclusion: The results of the present study imply that a highly significant reduction in CFU/ml count was found in subgroup A1. Therefore, within the limitations of the present in-vivo study, Octenidine dihydrochloride can be recommended as an effective root canal irrigant than Artemisia annua plant extract.

Photodynamic Therapy for the Treatment of Infected Leg Ulcers—A Pilot Study

Chronic and infected leg ulcers (LUs) are painful, debilitating, resistant to antibiotics, and immensely reduce a patient’s quality of life. The purpose of our study was to demonstrate the efficacy of photodynamic therapy (PDT) for the treatment of infected chronic LUs. Patients were randomized into two experimental groups: the first group received 5-aminolevulinic acid photodynamic therapy (ALA-PDT) (10 patients), and the second group of 10 patients received local octenidine dihydrochloride (Octenilin gel) exposed to a placebo light source with an inserted filter that mimiced red light. In the PDT group, we used 20% ALA topically applied for 4 hrs and irradiation from a Diomed laser source with a wavelength of 630 nm at a fluency of 80 J/cm2. ALA-PDT was performed 10 times during a 14-day hospitalization in 10 patients of both sexes aged 40–85 years with chronic leg ulcers. Treatments were carried out at 3-week intervals for 3–5 cycles. At 8-month follow-up with the PDT group, complete remission (CR) was obtained in four patients (40%), partial response (>50% reduction in ulcer diameter) in four patients (40%), and no response in two patients (20%) who additionally developed deterioration of the local condition with swelling, erythema, and inflammation. To assess the degree of pain during the trials, we used a numeric rating scale (NRS). From the preliminary results obtained, we concluded that PDT can be used to treat leg ulcers as a minimally invasive and effective method with no serious side effects, although further studies on a larger group of patients with LUs are warranted.