Drug delivery systems for prolonged duration local anesthesia

Abstract

Numerous drug delivery systems have been applied to the problem of providing prolonged duration local anesthesia (PDLA). Here we review the rationale for PDLA, the desirable features for and important attributes of such systems, and specific examples that have been developed.

Getting Drugs Across Biological Barriers

“…Nanoscale liposomes (vesicular structures composed of lipids [190] ) have demonstrated better skin penetration than most other nanoparticles. [191] Liposomes with the structural flexibility to deform and squeeze through the intercellular lipid bilayers demonstrated greater skin penetration than rigid liposomes.…”

Watching the gorilla and questioning delivery dogma

“…The sustained, constant release of therapeutic peptides and proteins offers tremendous advantages in terms of efficacy and patient compliance [42]. Despite the consistent, decades- long effort to develop sustained release protein formulations, the syringe and the pump remain the only delivery systems currently marketed for protein delivery.…”

“…Furthermore, it should be understood that instability is a fundamental barrier to the incorporation of proteins (e.g., interferons and growth factors) into any material (e.g., drug delivery systems, hydrogels for tissue engineering) [43–49]. Practically speaking, the significant and fundamental differences between small molecule therapeutics and proteins in terms of chemical stability, potential for immunogenicity, aggregation, and structural perturbation impose a formidable barrier to the development of protein delivery systems [41, 42]. …”

Advances of Nano-Structured Extended-Release Local Anesthetics

“…Compared to macro-scaled drug delivery systems (DDSs), nano-scaled DDS is more compatible to nanostructured biological environment which facilitates its cellular penetration, better bioavailability, and longer retention time [4]. With advances of manufacture techniques, nano-scaled DDS have achieved prominent success in extended-release, which show improved loading efficiency, better biocompatibility (acceptable local inflammation such as myotoxicity and neurotoxicity), and biodegradability (similar degradation rate with depletion of loaded compounds and assuring fully wearing off) [7][8][9]. Furthermore, adjustable and differentiated release profile (flexible duration, modulated analgesic intensity, and controlled targeted release by specific modifications) is designed to meet different demands [7,8].…”

“…With advances of manufacture techniques, nano-scaled DDS have achieved prominent success in extended-release, which show improved loading efficiency, better biocompatibility (acceptable local inflammation such as myotoxicity and neurotoxicity), and biodegradability (similar degradation rate with depletion of loaded compounds and assuring fully wearing off) [7][8][9]. Furthermore, adjustable and differentiated release profile (flexible duration, modulated analgesic intensity, and controlled targeted release by specific modifications) is designed to meet different demands [7,8]. Furthermore, diversity of materials are available for choice nowadays, greatly decreasing the cost and expanding the application of nano-scale DDS [7].…”