Date Published: December 8, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Edward A. Shipton.
Part 2 of this paper deals with the techniques for drug delivery of topical and injectable local anaesthetics. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous) are explored. To enhance transdermal local anaesthetic permeation, additional methods to the use of an eutectic mixture of local anaesthetics and the use of controlled heat can be used. These methods include iontophoresis, electroporation, sonophoresis, and magnetophoresis. The potential clinical uses of topical local anaesthetics are elucidated. Iontophoresis, the active transportation of a drug into the skin using a constant low-voltage direct current is discussed. It is desirable to prolong local anaesthetic blockade by extending its sensory component only. The optimal release and safety of the encapsulated local anaesthetic agents still need to be determined. The use of different delivery systems should provide the clinician with both an extended range and choice in the degree of prolongation of action of each agent.
A drug delivery system should have minimal tissue reaction, a reliable drug release profile, and well-defined degradation rate for biodegradable carrier until all nontoxic products are excreted . For local anaesthetics (LAs), the development of new effective delivery systems intends to suitably modulate the release rate of these drugs, extend their anaesthetic effect, and enhance their localisation; this reduces problems of systemic toxicity. Part 2 of this paper deals with the innovations pertaining to formulations, and techniques for drug delivery of topical and injectable local anaesthetics.
Transdermal drug delivery is one of the most patient-compliant routes of drug administration. However, the stratum corneum, the outer most layer of the skin resists the penetration of drugs across the skin (Figure 5). Hydrophilic, ionised, and macromolecular substances are poorly permeable across the skin . To enhance drug permeation in a passive manner, transdermal drugs should be lipophilic and should ideally have a molecular weight less than 500 Daltons . Alternatively, energy-dependent active measures can be used to enhance drug delivery across the skin. These include physical permeabilisation of skin or by driving the drug molecule across the skin. In addition to the use of an eutectic mixture of local anaesthetics, and the use of controlled heat, other methods such as iontophoresis, electroporation, sonophoresis, and magnetophoresis can be used .
Iontophoresis involves the active transportation of a drug into the skin using a constant low-voltage direct current. Ions migrate between electrodes of opposite charges, promoting ion transport through the skin (Figure 8) . A direct electrical current facilitates the dermal penetration of positively charged lignocaine molecules when placed under a positive electrode for local anaesthesia. Physicochemical properties, such as good aqueous solubility, and the presence of charged groups that render peptides and proteins “difficult to deliver” by other approaches, are ideal for iontophoresis  The amount of drug delivered via iontophoresis is dependent on the current and the duration of delivery. The control afforded by constant current iontophoresis over transport rates means that peptide/protein delivery kinetics could mimic endogenous secretion profiles . Moreover, complex input kinetics can be used to optimise and individualise therapy.
It is desirable to acquire the ability to prolong local anaesthetic blockade and, if possible, extend only its sensory component. This paper portrayed the innovative techniques for the drug delivery of topical and injectable local anaesthetics. However, the optimal release and safety of the encapsulated LA agents still need to be determined. Using encapsulation to avoid systemic toxicity, the nonconventional local anaesthetics (tetrodotoxin, saxitoxin) show promising efficacy . Recently, lignocaine-coated microneedles have been developed for rapid, safe, and prolonged local analgesic action . These delivery systems should provide the clinician with both an extended range and a choice in the degree of prolongation of action of each agent .