Liposomal delivery system for topical anaesthesia of the palatal mucosa

Abstract

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.

Introduction

Local anaesthesia of the palatal mucosa is important to enable manipulation of palatal soft tissue without pain during dental procedures.¹ However, this region has a thick, keratinised layer that is more resistant to the effects of topical anaesthetics than other intraoral sites, mainly the anterior region.2, 3 Infiltration of anaesthetic into the palatal mucosa can be extremely painful because the mucosa is firmly attached to the underlying periosteum and has numerous accessory nerves.⁴ According to Harker, the pain during palatal injections is more associated with the dislocation of the mucoperiosteum than with the puncture.⁵ Because palatal mucosa is one of the most painful sites to anaesthetise locally, it is the strictest test to which a topical anaesthetic can be submitted to assess its efficacy.3, 6

An effective topical agent to reduce pain during local anaesthesia in the palate has been sought since 1979.⁷ Several studies have shown that the most used topical agent, 20% benzocaine, failed to reduce pain from insertion of a needle and from an injection of local anaesthetic in this region.7, 8, 9, 10

The first studies of EMLA, the eutectic mixture of 2.5% lidocaine and 2.5% prilocaine for dermal use, that were made on the oral mucosa showed promising results. In most the cream was effective on the palatal mucosa in alleviating pain from insertion of a needle,6, 11, 12, 13 injection of a local anaesthetic,9, 14 and removal of a leaf fibroma.¹⁵ According to Meechan this was the unique effective topical anaesthetic with which to reduce pain during palatal injection.²

The liposomal encapsulation of local anaesthetics has been widely studied for dermal topical application. Liposomes are phospholipid vesicles used to carry drugs that have been shown to increase cutaneous and percutaneous penetration, provide slow release of the local anaesthetic, and better superficial anaesthesia.16, 17, 18, 19, 20 In the oral mucosa the liposomal encapsulated ropivacaine was of similar efficacy to EMLA in reducing pain during insertion of a needle into the maxillary buccal fold after a 2-min application.²¹

The aim of the current study was to evaluate the efficacy of liposomal encapsulated ropivacaine at different concentrations in reducing pain during insertion of a needle and injection of a local anaesthetic into the palatal mucosa.