José Ranali

Micro and nanosystems for delivering local anesthetics

Introduction: One of the most common strategies for pain control during and after surgical procedures is the use of local anesthetics. Prolonged analgesia can be safely achieved with drug delivery systems suitably chosen for each local anesthetic agent. Areas covered: This review considers drug delivery formulations of local anesthetics designed to prolong the anesthetic effect and decrease toxicity. The topics comprise the main drug delivery carrier systems (liposomes, biopolymers, and cyclodextrins) for infiltrative administration of local anesthetics. A chronological review of the literature is presented, including details of formulations as well as the advantages and pitfalls of each carrier system. The review also highlights pharmacokinetic data on such formulations, and gives an overview of the clinical studies published so far concerning pain control in medicine and dentistry. Expert opinion: The design of novel drug delivery systems for local anesthetics must focus on how to achieve higher uploads of the anesthetic into the carrier, and how to sustain its release. This comprehensive review should be useful to provide the reader with the current state-of-art regarding drug delivery formulations for local anesthetics and their possible clinical applications.

Liposome-encapsulated ropivacaine for topical anesthesia of human oral mucosa.

BACKGROUND:The elimination of pain caused by needle insertion for local anesthesia would be a significant advance in dentistry. METHODS:In this blinded cross-over study we evaluated the efficacy of liposome-encapsulated ropivacaine for topical anesthesia. Thirty healthy volunteers received 60 mg topical anesthetics: Liposome-encapsulated 1% ropivacaine, 1% plain ropivacaine, 2.5% lidocaine and 2.5% prilocaine mixture (EMLA), and 20% benzocaine gel, in the buccal fold of the upper-right canine for 2 min in different sessions. After insertion of 30-G needles, pain was rated on a visual analog scale (VAS). A pinprick test was used to measure the duration of topical anesthesia. The pulpar response was assessed by an electric pulp tester. RESULTS:VAS median and interquartile range (in cm) were 0.8 (0.4–1.5), 1.6 (0.8–2.6), 1.1 (0.3–2.7), 2.2 (0.9–2.9) for liposome-encapsulated ropivacaine, ropivacaine, EMLA, and benzocaine groups, respectively. The liposome-encapsulated ropivacaine group showed lower VAS mean values when compared with the benzocaine group (P = 0.0205). The median values and interquartile range for the duration of soft tissue anesthesia were 11 (7–14), 6.5 (4–11), 14 (11–16), and 7 (6–9) min for liposome-encapsulated ropivacaine, ropivacaine, EMLA, and benzocaine groups, respectively. EMLA and liposome-encapsulated ropivacaine were just as efficient for reducing pain, and showed longer soft tissue anesthesia when compared to the other local anesthetics (P = 0.0001). CONCLUSION:Liposomal-encapsulated 1% ropivacaine gel was equivalent to EMLA® for reducing pain during needle insertion and for the duration of soft tissue anesthesia. None of the topical anesthetics was effective for inducing pulpal anesthesia.

Anesthetic Efficacy of Articaine and Lidocaine for Incisive/Mental Nerve Block

INTRODUCTION The incisive/mental nerve block (IMNB) could be an alternative to the inferior alveolar nerve block in the mandibular anterior teeth. The effectiveness of articaine has not been tested in IMNB. METHODS This prospective randomized double-blind crossover study compared the anesthetic efficacy of 0.6 mL 4% articaine and 2% lidocaine, both with 1:100.000 epinephrine administered as IMNB to 40 volunteers in two sessions. Pulpal anesthesia of lateral incisor through premolars was tested with an electric pulp tester. The injection and postoperative pain were evaluated by using visual analog scales. The onset (time from the end of injection to the absence of pulpal response) and duration of pulpal anesthesia (time recorded before two positive responses to the pulp tester) and the anesthesia success (two consecutive readings of 80 without response and onset<or=10 minutes) were measured. RESULTS Articaine provided a higher success rate (p<0.001) of anesthesia than lidocaine for the lateral incisor (32.5%), the canine (55%), and the first (72.5%) and second (80%) premolars and a faster onset (p<0.05) for canine and increased duration (p<0.05) of anesthesia for premolars. The median duration of premolars anesthesia was 10 and 20 minutes, respectively, with lidocaine and articaine. There were no differences in pain scores between the solutions (p>0.05). CONCLUSIONS Articaine promoted higher anesthesia success and longer duration of anesthesia than lidocaine for most of the teeth after IMNB although anesthesia success could be considered clinically appropriated only for premolars. The volume of local anesthetic used in the present study may not be appropriate for procedures lasting longer than 10 minutes.

Anesthetic Efficacy of Bupivacaine Solutions in Inferior Alveolar Nerve Block

The purpose of this study was to compare the anesthetic efficacy of 2 bupivacaine solutions. Twenty-two volunteers randomly received in a crossover, double-blinded manner 2 inferior alveolar nerve blocks with 1.8 mL of racemic bupivacaine and a mixture of 75% levobupivacaine and 25% dextrobupivacaine, both 0.5% and with 1 : 200,000 epinephrine. Before and after the injection, the first mandibular premolar was evaluated every 2 minutes until no response to the maximal output (80 reading) of the pulp tester and then again every 20 minutes. Data were analyzed using the Wilcoxon paired test and the paired t test. No differences were found between the solutions for onset and duration of pulpal anesthesia and duration of soft tissue anesthesia (P > .05). It was concluded that the solutions have similar anesthetic efficacy.

Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects

OBJECTIVE The aim of this study was to compare the cardiovascular effects and the anesthetic efficacy of intraosseous injections of 4% articaine with 1:100,000 epinephrine (EPI100) or 4% articaine with 1:200,000 epinephrine (EPI200). STUDY DESIGN In this prospective, randomized, double-blind study, 0.9 mL EPI100 and EPI200 solutions were administered for endodontic treatment of mandibular molars with symptomatic irreversible pulpitis in 60 patients. The anesthetic success and pain during anesthesia were evaluated by visual analog scale. The cardiovascular parameters evaluated were heart rate, diastolic/systolic blood pressure, pulse oximetry, and electrocardiogram changes. RESULTS Both solutions provided high anesthetic efficacy (96.8% and 93.1% for EPI100 and EPI200, respectively; P > .05), and the cardiovascular parameters showed minimal incidences of significant differences throughout the clinical procedure. CONCLUSIONS The epinephrine concentration did not affect the efficacy of 4% articaine, and both solutions produced a high success level of pulpal anesthesia. Intraosseous delivery by slow speed of injection did not induce significant clinical changes in cardiovascular parameters.

Anesthetic Efficacy of 3 Volumes of Lidocaine With Epinephrine in Maxillary Infiltration Anesthesia

The objective of this randomized double-blind investigation was to compare the anesthetic efficacy and injection discomfort of 3 volumes of 2% lidocaine with 1:100,000 epinephrine for maxillary infiltration anesthesia. A total of 25 subjects received 0.6, 0.9, and 1.2 mL of the anesthetic buccal to an upper canine. Test teeth were assessed with electrical stimulation to determine onset and duration of pulpal anesthesia; soft tissue anesthesia and injection discomfort were assessed by pin-prick test and visual analog scale (VAS). Data were analyzed by 2-way analysis of variance (ANOVA), Friedman, and chi-square tests (alpha = 5%). The 1.2 mL dose induced faster onset of pulpal anesthesia, a higher success rate, and a longer duration of soft tissue/pulpal anesthesia than were achieved with the other doses (P < .05). No differences in injection discomfort were observed between treatments. It is concluded that maxillary infiltration anesthesia with lidocaine and epinephrine has a faster onset, a greater success rate, and a longer duration when a volume of 1.2 mL is used than when volumes less than 1.0 mL are used.

Liposomal delivery system for topical anaesthesia of the palatal mucosa

An effective topical agent to reduce pain during local anaesthesia of the palate is not yet available. The aim of the present study was to evaluate the efficiency of liposome-encapsulated ropivacaine in different concentrations for topical anaesthesia of the palatal mucosa. In this single-blinded, placebo-controlled, crossover study 40 (20 male) healthy volunteers were randomised to be given: liposome-encapsulated 2% ropivacaine, liposome-encapsulated 1% ropivacaine, a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA), and liposomal placebo gel, topically on to the palatal mucosa of the right canine region for 5 min each, at four different sessions. Pain associated with insertion of a 30G needle, and with injection of a local anaesthetic, was rated on a visual analogue scale (VAS). The effect of liposomal ropivacaine 1% and 2% did not differ from that of placebo (p=0.3 and p=0.1, respectively) in reducing pain during insertion of the needle. Lower VAS were obtained with EMLA. In this group VAS were lower in women than men (p=0.007). There was no difference in VAS among groups (p=0.3) as far as injection of the local anaesthetic was concerned. In conclusion, liposomal-encapsulated ropivacaine formulations did not reduce the pain of insertion of a needle into the palatal mucosa. None of the anaesthetic formulations tested, including the positive control (EMLA), were effective in reducing the pain of an injection of local anaesthetic compared with placebo.

Liposome-encapsulated ropivacaine for intraoral topical anesthesia.

OBJECTIVES This study evaluated the efficacy of liposome-encapsulated 2% ropivacaine in topical anesthesia and its influence on pulpal response. STUDY DESIGN 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. RESULTS RL2 and B20 showed lower pain response to needle insertion and longer soft tissue anesthesia then P and LP (P = .0003 and P < .0001, respectively); however, RL2 was not different from B20 (P > .05) regarding those parameters. None of the formulations was able to induce pulpal anesthesia. CONCLUSION 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.

Efficacy of liposome-encapsulated mepivacaine for infiltrative anesthesia in volunteers.

This blinded crossover study evaluated the efficacy and pain sensitivity evoked by a previously reported liposome-encapsulated mepivacaine formulation (). Thirty healthy volunteers received an intraoral injection (1.8 mL), at four different sessions, of the following formulations: 2% mepivacaine with 1:100,000 epinephrine (MVC2%EPI), 3% mepivacaine (MVC3%), and 2 and 3% liposome-encapsulated mepivacaine (MVC2%LUV and MVC3%LUV). Latency period and duration of anesthesia were assessed by an electrical pulp tester and injection discomfort by a visual analog scale (VAS). Data were analyzed with Tukey-Kramer and Friedman tests (P < 0.05). No significant difference was found regarding latency period (in minutes) among the formulations (P > 0.05). The duration of anesthesia after the injection of MVC3%LUV was higher than the one obtained after the infiltration of MVC2%LUV and of MVC3% (P < 0.05). However, the duration of anesthesia obtained with MVC3% did not differ from the one obtained with MVC2%LUV (P > 0.05). MVC3%LUV showed lower VAS median values than MVC2%EPI (P < 0.05), and there were no significant differences among the others formulations. Liposome-encapsulated 3% mepivacaine showed longer duration of anesthesia, in comparison to the commercial formulation of MVC3%. MVC2%LUV was able to produce a similar duration of anesthesia as the 3% commercial formulation, despite the 50% decrease in the anesthetic concentration. Thus, the encapsulation of mepivacaine increased the duration of anesthesia and reduced the injection discomfort caused by vasoconstrictor-associated formulations in healthy volunteers.

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.