What Pharmacists Should Know About Advances in Topical Delivery Systems for Lidocaine

What Pharmacists Should Know About Advances in Topical Delivery Systems for Lidocaine

i-microscopeWhen lidocaine was first discovered—an unexpected find in the quest to identify genetic differences in barley plants—its Swedish founder realized it had a slight anesthetic impact, but set it aside as being less effective than the main drug of the day, procaine. As World War II raged and front-line medics desperately needed anesthetics, the new substance was re-tested, revealing it actually lasted longer than procaine.

Since then, lidocaine’s uses have expanded to include migraine relief and treating skin conditions, heart arrhythmias and bladder pain. Along the way, topical delivery systems have also progressed, boosting lidocaine’s therapeutic value. Now another change is taking place—one poised to have the biggest impact of all: nanoparticle delivery systems.

Lidocaine-Loaded Nanostructured Lipid Carriers

Lidocaine’s founder probably never imagined working on nanoscale molecules.1 In the emerging field of nanotechnology, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two of the most researched delivery systems for lipophilic drugs. SLNs were developed to solve limitations encountered with other colloidal carriers, such as liposomes and polymeric nanoparticles. But SLNs also had some shortcomings, notably limited drug-loading and a tendency to discharge the drug during storage.2 As a result, second-generation lipid carriers were developed—NLCs—with improved capacity and stability.

Lidocaine has joined a handful of other drugs as one of the first topical applications to be studied in this new age of NLCs. Although a significant amount of future research is still needed, a study published in the April 2016 issue of Drug Delivery produced promising results when NLCs were used to enhance topical absorption of lidocaine. The researchers developed the topical anesthetic by loading NLCs with transcriptional transactivator peptide (TAT) modified lidocaine (TAT-NLCs-LID). Skin permeation was examined in vitro using a Franz diffusion cell mounted with depilated mouse skin. Anesthesia was also evaluated in vivo using mice. Compared with the control—TAT conjugated with DSPE-PEG(2000) Malemide—the NLC delivery system achieved the following results:3

  • TAT-NLCs-LID had a substantially smaller mean diameter of 157.9 nanometers
  • TAT-NLCs-LID had 81 percent higher encapsulation
  • Transdermal flux of TAT-NLCs-LID was several times higher
  • Overall pain threshold was reduced

Different methods for developing nanoparticles are also under scrutiny, as experts work to discover the best methods and how each one works with different pharmaceuticals. The layer-by-layer technique creates nanoparticles just as it says—in multiple layers—which can be used to control the release rate or to combine multiple drugs. Transdermal delivery of lidocaine has been tested using a layer-by-layer technique of chitosan and hyaluronic acid, which was then loaded into NLCs. This nanoparticle exhibited good skin permeation and a prolonged anesthetic effect.4

Polymeric Liposomes Enhance Topical Delivery Systems for Lidocaine

NLCs aren’t the only nanoplatforms with the ability to boost topical absorption of lidocaine. In spite of limitations when compared with NLCs, liposomes still have their own unique advantages. Liposomes consist of a spherical bilayer surrounding the therapeutic drug tucked into an aqueous core. Different agents can be added to the lipid membrane to alter surface chemistry and properties such as size, charge and functionality. This means that liposomes can be customized to reduce drug toxicity. It also makes them a highly effective method for targeted systemic delivery.5 As a result, research has focused on using liposome technology with chemotherapeutic agents.

Polymeric liposomes loaded with lidocaine offer another topical delivery system option. In one study, polymeric liposomes were developed by conjugating TAT-modified lidocaine with octadecyl-quaternized, lysine-modified chitosans (LID-TAT-PLs), reported the International Journal of Pharmaceutics.6 Like the studies using NLCs, particle size, morphology and the efficiency of drug encapsulation were verified, then skin permeation was tested using a Franz diffusion cell. Compared to conventional liposomes, LID-TAT-PLs had a substantially smaller diameter, higher encapsulation efficiency, better stability, and more than double transdermal flux.

Researchers emphasized the value of nanoparticles by comparing a lidocaine-loaded lipid-polymer hybrid with lidocaine-loaded conventional liposomes. The hybrid nanoparticles delivered significantly better in vitro skin permeation and in vivo local anesthetic effects. The conclusion stated in Drug Delivery speaks for all the studies—nanoparticles safely improve the topical absorption and effectiveness of lidocaine.7

Alternative Delivery Systems

While nanotechnology gets a lot of press, other topical delivery methods are also on the horizon for lidocaine:

  • Bacterial cellulose membranes: This biomaterial adheres to irregular skin surfaces and early studies show it can modulate the bioavailability of lidocaine as a topical or transdermal delivery system.8
  • Oral mucosal patch: When a bioadhesive made from lidocaine hydrochloride five percent on a polyvinyl pirrolidone K90, 1,2-propylenglycol and water patch was applied to porcine oral mucosa, 5.7 percent of the lidocaine was deposited on the mucosal tissue and 5.3 percent permeated over 8 hours. Such a patch could be cut to fit dosage and the size of the application area.9

Time to Look Forward and Anticipate Lidocaine’s Influence

At the dawn of advances like nanotechnology, all bets are off—projections about progress, clinical trials and commercialization are nearly impossible to evaluate. One estimate suggests that nanotechnology has the potential to affect about half of the worldwide drug production over the next decade, representing roughly $380 billion in revenue. One thing is certain: any technology that improves topical delivery stands to boost the influence of lidocaine.

Pharmaceutica North America provides lidocaine ointment USP 5 percent and lidocaine hydrochloride, along with a broad selection of other high-quality prescription products and APIs. We stay up-to-date with the latest research and emerging products, so contact us today to talk about how we can help meet your patient’s needs.

Show 9 footnotes

  1. “Lidocaine: The Origin of a Modern Local Anesthetic,” December 2010, http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2085799#68704665
  2. “Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application,” September 2015, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616893/
  3. “Transcriptional Transactivator Peptide Modified Lidocaine-loaded Nanoparticulate Drug Delivery System for Topical Anesthetic Therapy, April 2016, http://www.ncbi.nlm.nih.gov/pubmed/27045388
  4. “Local Anesthetic Lidocaine Delivery System: Chitosan and Hyaluronic Acid Modified Layer-by-Layer Lipid Nanoparticles,” June 2016, http://www.ncbi.nlm.nih.gov/pubmed/27340888
  5. “Nanotechnology in Therapeutics,” 2012, http://www.medscape.com/viewarticle/770397
  6. “Preparation and Evaluation of Lidocaine Hydrochloride-Loaded TAT-conjugated Polymeric Liposomes for Transdermal Delivery,” January 2013, http://www.ncbi.nlm.nih.gov/pubmed/23089577
  7. “An Alternative Choice of Lidocaine-Loaded Liposomes: Lidocaine-Loaded Lipid-Polymer Hybrid Nanoparticles for Local Anesthetic Therapy,” May 2016, http://www.ncbi.nlm.nih.gov/pubmed/26881926
  8. “Bacterial Cellulose Membranes Applied in Topical and Transdermal Delivery of Lidocaine Hydrochloride and Ibuprofen: In Vitro Diffusion Studies,” October 2012, http://www.ncbi.nlm.nih.gov/pubmed/22266531
  9. “Development and Evaluation of a Bioadhesive System for Oral Mucosa Delivery of Lidocaine Hydrochloride,” August 2013, https://www.researchgate.net/profile/Cesar_Serna_Jimenez/publication/263920074_Development_and_Evaluation_of_a_Bioadhesive_System_for_Oral_Mucosa_Delivery_of_Lidocaine_Hydrochloride/links/02e7e53c51c1472eff000000.pdf
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