Recent advances and perspectives in topical oral anesthesia

ABSTRACT

Introduction: Topical anesthesia is widely used in dentistry to reduce pain caused by needle insertion and injection of the anesthetic. However, successful anesthesia is not always achieved using the formulations that are currently commercially available. As a result, local anesthesia is still one of the procedures that is most feared by dental patients. Drug delivery systems (DDSs) provide ways of improving the efficacy of topical agents.

Areas covered: An overview of the structure and permeability of oral mucosa is given, followed by a review of DDSs designed for dental topical anesthesia and their related clinical trials. Chemical approaches to enhance permeation and anesthesia efficacy, or to promote superficial anesthesia, include nanostructured carriers (liposomes, cyclodextrins, polymeric nanoparticle systems, solid lipid nanoparticles, and nanostructured lipid carriers) and different pharmaceutical dosage forms (patches, bio- and mucoadhesive systems, and hydrogels). Physical methods include pre-cooling, vibration, iontophoresis, and microneedle arrays.

Expert opinion: The combination of different chemical and physical methods is an attractive option for effective topical anesthesia in oral mucosa. This comprehensive review should provide the readers with the most relevant options currently available to assist pain-free dental anesthesia. The findings should be considered for future clinical trials.

KEYWORDS:

• Dentistry
• drug delivery systems
• oral mucosa
• dental topical anesthesia
• dentistry
• liposomes
• cyclodextrins
• nanoparticles
• buccal films

Article highlights

• Topical anesthesia offers the possibility of pain-free dental anesthesia.

• The greatest challenge in formulation development is to overcome the oral mucosa epithelium barrier, wrongly considered a highly permeable tissue.

• Although there are several studies reporting formulation development and promising in vitro performance, only a few formulations have been evaluated in clinical trials.

• All the clinical trials involving chemical methods (DDSs and pharmaceutical dosage forms) described throughout the review are summarized in Table 1. Nine studies are highlighted because they evaluated formulations still under development (not yet commercially available), in Phase I clinical trials. Seven of these tested liposomal formulations and two used polymeric films.

• Clinical trials indicate that liposomal encapsulation and the pre-cooling technique promote improved topical anesthetic efficacy in different oral mucosa sites, including the palatal mucosa, and seem to be auspicious strategies in dental topical anesthesia.

• Further studies are needed to evaluate the effectiveness of combinations of different chemical and physical methods, since this represents the most promising option for overcoming topical anesthesia challenges.

This box summarizes key points contained in the article.

Acknowledgments

The authors are grateful to Felipe Blanco for preparation of the Figures.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Financial support for this work was provided by the São Paulo Research Foundation (FAPESP, grants 2012/06974-4 and 2014/14457-5).