Capsaicin cyclodextrin complex enhances mepivacaine targeting and improves local anesthesia in inflamed tissues

Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics LA . Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin CAP triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two drug combination LA and CAP on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl beta cyclodextrin HP amp; 946; CD , as shown by the phase solubility study. The resulting complex HP amp; 946; CD CAP showed 1 1 stoichiometry and high association constant, according to phase solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry DSC , X ray diffraction, and 1H NMR. The freeze dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2 mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug deliver

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The Effect Of Combined Bleaching Techniques On Oral Microbiota

Aims : To evaluate the antimicrobial activity of 10% and 37% carbamide peroxide during dental bleaching in three different modes. Materials and Methods : This five-week double-blind randomized controlled trial included 32 volunteers assigned to four groups (n = 8). Each group received bleaching agents or placebo as an in-office and at-home treatment. The dental bleaching techniques were: In-office bleaching (37% carbamide peroxide: CP37); at-home bleaching (10% carbamide peroxide: CP10) and the association of both (CP37 and CP10). Saliva samples were collected right before (baseline), right after, 12 hours after, and seven days after the treatment. Counts of total microorganisms, Streptococci, and Mutans streptococci were carried out. Friedman test ( = 0.05) was used to compare the microorganism counts. Results : The number of the all oral microorganisms remained stable during all experiment. Conclusions : No bleaching agent (CP37, CP10 or the combination of both) was able to reduce the oral microorganisms tested.203304307Sulieman, M., An overview of bleaching techniques: 2, Night guard vital bleaching and nonvital bleaching (2006) SADJ, 61, pp. 352-354. , 356Kihn, P.W., Vital tooth whitening (2007) Dent Clin North Am, 51, pp. 319-331. , viiiHaywood, V.B., Heymann, H.O., Nightguard vital bleaching (1989) Quintessence Int, 20, pp. 173-176Leonard Jr., R.H., Bentley, C., Eagle, J.C., Garland, G.E., Knight, M.C., Phillips, C., Nightguard vital bleaching: A long-term study on efficacy, shade retention side effects, and patients. Perceptions (2001) J Esthet Restor Dent, 13, pp. 357-369Fiedler, R.S., Reichl, R.B., Combined professional and home care nightguard bleaching of tetracycline-stained teeth (2000) Gen Dent, 48, pp. 257-261Gurgan, S., Bolay, S., Alaçam, R., Antibacterial activity of 10% carbamide peroxide bleaching agents (1996) J Endod, 22, pp. 356-357Bentley, C.D., Leonard, R.H., Crawford, J.J., Effect of whitening agents containing carbamide peroxide on cariogenic bacteria (2000) J Esthet Dent, 12, pp. 33-37Alkmin, Y.T., Sartorelli, R., Flório, F.M., Basting, R.T., Comparative study of the effects of two bleaching agents on oral microbiota (2005) Oper Dent, 30, pp. 417-423Dasanayake, A.P., Caufield, P.W., Cutter, G.R., Roseman, J.M., Köhler, B., Differences in the detection and enumeration of mutans streptococci due to differences in methods (1995) Arch Oral Biol, 40, pp. 345-351Groppo, F.C., Ramacciato, J.C., Simões, R.P., Flório, F.M., Sartoratto, A., Antimicrobial activity of garlic, tea tree oil, and chlorhexidine against oral microorganisms (2002) Int Dent J., 52, pp. 433-437Gold, O.G., Jordan, H.V., Van Houte, J., A selective medium for Streptococcus mutans (1973) Arch Oral Biol, 18, pp. 1357-1364Marshall, M.V., Cancro, L.P., Fischman, S.L., Hydrogen peroxide: A review of its use in dentistry (1995) J Periodontol, 66, pp. 786-796Li, Y., Toxicological considerations of tooth bleaching using peroxide- containing agents (1997) J Am Dent Assoc, 128, pp. 31S-36STredwin, C.J., Naik, S., Lewis, N.J., Scully, C., Hydrogen peroxide tooth- whitening (bleaching) products: Review of adverse effects and safety issues (2006) Br Dent J, 200, pp. 371-376Imlay, J.A., How oxygen damages microbes: Oxygen tolerance and obligate anaerobiosis (2002) Adv Microb Physiol, 46, pp. 111-153Scherer, W., Boylan, R., Bhatt, S., Vital bleaching agents and oral antiseptic: Effect on anaerobic bacteria (1992) J Esthet Dent, 4, pp. 84-85Gautier, G., Noguer, M., Costa, N., Canela, J., Viñas, M., Mouthrinses: A comparative microbiological study (2000) Bull Group Int Rech Sci Stomatol Odontol, 42, pp. 23-29Ryan, C.S., Kleinberg, I., Bacteria in human mouths involved in the production and utilization of hydrogen peroxide (1995) Arch Oral Biol, 40, pp. 753-763Lemos, J.A., Abranches, J., Burne, R.A., Responses of cariogenic streptococci to environmental stresses (2005) Curr Issues Mol Biol, 7, pp. 95-107Marquis, R.E., Oxygen metabolism, oxidative stress and acid-base physiology of dental plaque biofilms (1995) J Ind Microbiol, 15, pp. 198-207Carlsson, J., Salivary peroxidase: An important part of our defense against oxygen toxicity (1987) J Oral Pathol, 16, pp. 412-416Thomas, E.L., Milligan, T.W., Joyner, R.E., Jefferson, M.M., Antibacterial activity of hydrogen peroxide and the lactoperoxidase- hydrogen peroxide-thiocyanate system against oral streptococci (1994) Infect Immun, 62, pp. 529-535Steinberg, D., Heling, I., Daniel, I., Ginsburg, I., Antibacterial synergistic effect of chlorhexidine and hydrogen peroxide against Streptococcus sobrinus, Streptococcus faecalis and Staphylococcus aureus (1999) J Oral Rehabil, 26, pp. 151-15

Ulceration of gingival mucosa after topical application of EMLA: report of four cases

This study reports four cases of mucosa ulceration after a 30-minute application of EMLA (0.3 g) as a topical anaesthetic in dentistry. The subjects returned the next day with a white ulceration and desquamation on the application site. EMLA cream should not be applied to the oral mucosa for 30 minutes.204313313

Liposomal encapsulation improves the duration of soft tissue anesthesia but does not induce pulpal anesthesia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Study Objective: To compare the topical and the pulpal anesthesia efficacy of liposomal and plain benzocaine formulations Design: Double-blinded, randomized crossover study. Setting: University ambulatory dental center Patients: 30 ASA physical status 1 volunteers Interventions: Volunteers received, in three different sessions, topical application of liposome-encapsulated 10% benzocaine (LB10), 10% benzocaine gel (B10), and 20% benzocaine gel (B20) in the right maxillary canine mucobuccal fold Measurements: Pain associated with the needle insertion was rated by visual analog scale (VAS) and the duration of topical anesthesia was recorded Pulpal anesthesia was evaluated using an electric pulp tester Main Results: VAS values (median. 1st - 3rd quartiles) were 17 cm (11 - 25), 14 cm (3 - 22), and 21 cm (9 21) for B10, LB10, and 1320, respectively No differences were noted among the groups (Friedman test, P = 0 58) Soft tissue anesthesia was also not different The LB10 [10 (8 - 12) min] showed longer soft tissue anesthesia (Friedman test, P < 0 01) than the other agents [1310 = 8 (5 - 10) min, and B20 = 7 (6 - 9) min] None of the topical benzocaine formulations tested induced pulpal anesthesia Conclusions: The encapsulation of benzocaine into liposome increased the duration of soft tissue anesthesia However, it did not induce pulpal anesthesia (C) 2010 Elsevier Inc All rights reserved225313317DFL Ind Corn Ltda, Rio de Janeiro, BrazilConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Development Of Egg Pc/cholesterol ?-tocopherol Liposomes With Ionic Gradients To Deliver Ropivacaine.

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Efficacy of 1% ropivacaine gel for topical anesthesia of human oral mucosa

Objective: To evaluate the efficacy of 1 % ropivacaine for topical anesthesia in dentistry. Method and Materials: Thirty healthy volunteers randomly (blind crossover) received the following treatments: 20 mg of 1% ropivacaine gel (ropivacaine-20), 60 mg of 1% ropivacaine gel (ropivacaine-60), 20 mg of the eutectic mixture of local anesthetics 2.5% lidocaine and 2.5% prilocaine (EMLA cream, AstraZeneca; EMLA-20), 60 mg of EMLA (EMLA-60), 20 mg of 20% benzocaine gel (Benzotop, DFL; benzocaine-20), and 60 mg of 20% benzocaine gel (benzocaine-60), applied on the maxillary buccal fold of the right canine at different sessions. Pain was assessed by visual analog scale (VAS) and 11-point box scale (BS-11) after the insertion of 30-gauge needles. Soft tissue anesthesia was measured by pinprick test. Data were analyzed by Friedman and Pearson correlation tests. Results: All the topical anesthetics evaluated showed similar performance in relation to the pain perceived after needle insertion (P > .05), and there were no significant differences among groups considering VAS or BS-11 (P = .177 and P = .179, respectively). The duration of soft tissue anesthesia was not statistically significantly different for ropivacaine-20, EMLA-20, benzocaine-20, ropivacaine-60, EMLA-60, and benzocaine-60, but EMLA-60 showed significantly longer duration than the other agents (P < .05). Conclusion: All topical anesthetics were similar in reducing pain to needle insertion. EMLA-60 promoted longer duration of soft tissue anesthesia.38760160

Validation of an HPLC method for the determination of dibucaine encapsulated in solid lipid nanoparticles and nanostructured lipid carriers

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICODibucaine (DBC), used mainly in topical formulations, is one of the most potent long-acting local anesthetics, but is also one of the more toxic. Recently, solid lipid nanoparticles and nanostructured lipid carriers have been attracting attention as promising drug delivery carriers. This study develops and validates an analytical HPLC method for quantifying the local anesthetic DBC associated to lipidic structures. Average sizes, polydispersion, surface charge and DBC encapsulation efficiency were analyzed. The DBC quantification was performed by using C18-reversed-phase column, a mobile phase with acetonitrile: triethylamine phosphate buffer and UV detection. The results show that the analytical methodology is accurate, reproducible and robust; the method was linear in the concentration range 1.5-30 mu g/mL with a high correlation coefficient (r = 0.999). The nanoparticles presented mean diameters around 200 nm and high encapsulation efficiency for DBC (over 70% for SLN and NLC samples). This methodology can be useful for quantifying DBC in different nanostructured carriers32913621369FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP [06/00121-9]2006/00121-9sem informaçã

Liposome-encapsulated ropivacaine for intraoral topical anesthesia

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThis study evaluated the efficacy of liposome-encapsulated 2% ropivacaine in topical anesthesia and its influence on pulpal response. Forty volunteers received the following topical formulations in the buccal fold of the maxillary lateral incisors region (bilaterally): liposome-encapsulated 2% ropivacaine gel (RL2); 20% benzocaine gel (B20); liposomal placebo gel (LP); and placebo gel (P). Formulations were kept in place for 30 minutes, during which time the teeth were electric pulp tested every 10 minutes. After this procedure, a dental needle was inserted until periosteum contact in the same site of topical application and pain was rated by a visual analog scale. Duration of soft tissue anesthesia was assessed by pinprick test. RL2 and B20 showed lower pain response to needle insertion and longer soft tissue anesthesia then P and LP (P = .0003 and P .05) regarding those parameters. None of the formulations was able to induce pulpal anesthesia. RL2 was as effective as B20 in reducing pain during needle insertion and inducing soft tissue anesthesia; however, neither one was able to induce pulpal anesthesia after a 30-min application. ClinicalTrials.gov NCT010545471106800804FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP [06/00121-9, 06/53255-2]2006/00121-9; 2006/53255-