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Prolonged Duration Local Anesthesia

Part of the Advances in Delivery Science and Technology book series (ADST)

Abstract

Acute and chronic pain are often treated with local anesthetic agents, whether by injection or topical application. “Conventional” agents (amino-ester and amino-amide local anesthetics) are limited by systemic and local toxicity as well as their short durations of action. For more than 30 years, prolonged duration local anesthesia (PDLA) has been the focus of intense scientific investigation with the goal of enhanced anesthetic duration following a single application. To this end, a broad array of methods has been employed, including the use of nonconventional agents with local anesthetic properties, addition of adjuvants, and controlled release delivery systems. This chapter reviews selected developments in the very extensive field of PDLA.

Keywords

  • Hyaluronic Acid
  • Local Anesthetic
  • Encapsulation Efficiency
  • Drug Loading
  • Tissue Reaction

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Fig. 28.1
Fig. 28.2
Fig. 28.3

References

  1. Wang GK, Quan C, Vladimirov M, Mok WM, Thalhammer JG (1995) Quaternary ammonium derivative of lidocaine as a long-acting local anesthetic. Anesthesiology 83(6):1293–1301

    CAS  PubMed  Google Scholar 

  2. Weiniger CF, Golovanevski M, Sokolsky-Papkov M, Domb AJ (2010) Review of prolonged local anesthetic action. Expert Opin Drug Deliv 7(6):737–752. doi:10.1517/17425241003767383

    CAS  PubMed  Google Scholar 

  3. Weiniger CF, Golovanevski L, Domb AJ, Ickowicz D (2012) Extended release formulations for local anaesthetic agents. Anaesthesia 67(8):906–916. doi:10.1111/j.1365-2044.2012.07168.x

    CAS  PubMed  Google Scholar 

  4. Wiles MD, Nathanson MH (2010) Local anaesthetics and adjuvants–future developments. Anaesthesia 65(Suppl 1):22–37. doi:10.1111/j.1365-2044.2009.06201.x

    CAS  PubMed  Google Scholar 

  5. Adams HJ, Blair MR Jr, Takman BH (1976) The local anesthetic activity of saxitoxin alone and with vasoconstrictor and local anesthetic agents. Arch Int Pharmacodyn Ther 224(2):275–282

    CAS  PubMed  Google Scholar 

  6. Adams HJ, Blair MR Jr, Takman BH (1976) The local anesthetic activity of tetrodotoxin alone and in combination with vasoconstrictors and local anesthetics. Anesth Analg 55(4):568–573

    CAS  PubMed  Google Scholar 

  7. Padera R, Bellas E, Tse JY, Hao D, Kohane DS (2008) Local myotoxicity from sustained release of bupivacaine from microparticles. Anesthesiology 108(5):921–928. doi:10.1097/ALN.0b013e31816c8a48

    CAS  PubMed  Google Scholar 

  8. Sokolsky-Papkov M, Golovanevski L, Domb AJ, Weiniger CF (2009) Prolonged local anesthetic action through slow release from poly (lactic acid co castor oil). Pharm Res 26(1):32–39. doi:10.1007/s11095-008-9699-8

    CAS  PubMed  Google Scholar 

  9. McAlvin JB, Reznor G, Shankarappa SA, Stefanescu CF, Kohane DS (2013) Local toxicity from local anesthetic polymeric microparticles. Anesth Analg 116(4):794–803

    CAS  PubMed  Google Scholar 

  10. McLure HA, Rubin AP (2005) Review of local anaesthetic agents. Minerva Anestesiol 71(3):59–74

    CAS  PubMed  Google Scholar 

  11. Shankarappa SA, Tsui JH, Kim KN, Reznor G, Dohlman JC, Langer R, Kohane DS (2012) Prolonged nerve blockade delays the onset of neuropathic pain. Proc Natl Acad Sci U S A 109(43):17555–17560. doi:10.1073/pnas.1214634109

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Weldon CB, Tsui JH, Shankarappa SA, Nguyen VT, Ma M, Anderson DG, Kohane DS (2012) Electrospun drug-eluting sutures for local anesthesia. J Control Release 161(3):903–909. doi:10.1016/j.jconrel.2012.05.021

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Strichartz GR, Sanchez V, Arthur GR, Chafetz R, Martin D (1990) Fundamental properties of local anesthetics. II. Measured octanol:buffer partition coefficients and pKa values of clinically used drugs. Anesth Analg 71(2):158–170

    CAS  PubMed  Google Scholar 

  14. Kohane DS (2007) Microparticles and nanoparticles for drug delivery. Biotechnol Bioeng 96(2):203–209. doi:10.1002/bit.21301

    CAS  PubMed  Google Scholar 

  15. Castillo J, Curley J, Hotz J, Uezono M, Tigner J, Chasin M, Wilder R, Langer R, Berde C (1996) Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres. Anesthesiology 85(5):1157–1166

    CAS  PubMed  Google Scholar 

  16. Kohane DS, Lipp M, Kinney RC, Lotan N, Langer R (2000) Sciatic nerve blockade with lipid-protein-sugar particles containing bupivacaine. Pharm Res 17(10):1243–1249

    CAS  PubMed  Google Scholar 

  17. Kohane DS, Smith SE, Louis DN, Colombo G, Ghoroghchian P, Hunfeld NG, Berde CB, Langer R (2003) Prolonged duration local anesthesia from tetrodotoxin-enhanced local anesthetic microspheres. Pain 104(1–2):415–421

    CAS  PubMed  Google Scholar 

  18. Epstein-Barash H, Shichor I, Kwon AH, Hall S, Lawlor MW, Langer R, Kohane DS (2009) Prolonged duration local anesthesia with minimal toxicity. Proc Natl Acad Sci U S A 106(17):7125–7130. doi:10.1073/pnas.0900598106

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Kohane DS, Yieh J, Lu NT, Langer R, Strichartz GR, Berde CB (1998) A re-examination of tetrodotoxin for prolonged duration local anesthesia. Anesthesiology 89(1):119–131

    CAS  PubMed  Google Scholar 

  20. Shankarappa SA, Sagie I, Tsui JH, Chiang HH, Stefanescu C, Zurakowski D, Kohane DS (2012) Duration and local toxicity of sciatic nerve blockade with coinjected site 1 sodium-channel blockers and quaternary lidocaine derivatives. Reg Anesth Pain Med 37(5):483–489. doi:10.1097/AAP.0b013e31826125b3

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Kohane DS, Kuang Y, Lu NT, Langer R, Strichartz GR, Berde CB (1999) Vanilloid receptor agonists potentiate the in vivo local anesthetic activity of percutaneously injected site 1 sodium channel blockers. Anesthesiology 90(2):524–534

    CAS  PubMed  Google Scholar 

  22. Kohane DS, Lu NT, Cairns BE, Berde CB (2001) Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block. Reg Anesth Pain Med 26(3):239–245. doi:10.1053/rapm.2001.23215

    CAS  PubMed  Google Scholar 

  23. Kohane DS, Lu NT, Crosa GA, Kuang Y, Berde CB (2001) High concentrations of adrenergic antagonists prolong sciatic nerve blockade by tetrodotoxin. Acta Anaesthesiol Scand 45(7):899–905

    CAS  PubMed  Google Scholar 

  24. Simons EJ, Bellas E, Lawlor MW, Kohane DS (2009) Effect of chemical permeation enhancers on nerve blockade. Mol Pharm 6(1):265–273. doi:10.1021/mp800167a

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Sagie I, Kohane DS (2010) Prolonged sensory-selective nerve blockade. Proc Natl Acad Sci U S A 107(8):3740–3745. doi:10.1073/pnas.0911542107

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Brandhonneur N, Dollo G, Ratajczak-Enselme M, Deniau AL, Chevanne F, Estebe JP, Legrand A, Le Corre P (2011) Ex vivo and in vivo diffusion of ropivacaine through spinal meninges: influence of absorption enhancers. Int J Pharm 404(1–2):36–41. doi:10.1016/j.ijpharm.2010.10.049

    CAS  PubMed  Google Scholar 

  27. Jia X, Colombo G, Padera R, Langer R, Kohane DS (2004) Prolongation of sciatic nerve blockade by in situ cross-linked hyaluronic acid. Biomaterials 25(19):4797–4804

    CAS  PubMed  Google Scholar 

  28. Kohane DS, Lipp M, Kinney RC, Anthony DC, Louis DN, Lotan N, Langer R (2002) Biocompatibility of lipid-protein-sugar particles containing bupivacaine in the epineurium. J Biomed Mater Res 59(3):450–459

    CAS  PubMed  Google Scholar 

  29. Pere P, Watanabe H, Pitkanen M, Wahlstrom T, Rosenberg PH (1993) Local myotoxicity of bupivacaine in rabbits after continuous supraclavicular brachial plexus block. Reg Anesth 18(5):304–307

    CAS  PubMed  Google Scholar 

  30. Zimmer C, Piepenbrink K, Riest G, Peters J (2007) Cardiotoxic and neurotoxic effects after accidental intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion. Anaesthesist 56(5):449–453. doi:10.1007/s00101-007-1147-3

    CAS  PubMed  Google Scholar 

  31. Yamashita A, Matsumoto M, Matsumoto S, Itoh M, Kawai K, Sakabe T (2003) A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits. Anesth Analg 97(2):512–519, table of contents

    CAS  PubMed  Google Scholar 

  32. Benoit PW, Belt WD (1970) Destruction and regeneration of skeletal muscle after treatment with a local anaesthetic, bupivacaine (Marcaine). J Anat 107(Pt 3):547–556

    CAS  PubMed  Google Scholar 

  33. Benoit PW, Belt WD (1972) Some effects of local anesthetic agents on skeletal muscle. Exp Neurol 34(2):264–278

    CAS  PubMed  Google Scholar 

  34. Yagiela JA, Benoit PW, Buoncristiani RD, Peters MP, Fort NF (1981) Comparison of myotoxic effects of lidocaine with epinephrine in rats and humans. Anesth Analg 60(7):471–480

    CAS  PubMed  Google Scholar 

  35. Foster AH, Carlson BM (1980) Myotoxicity of local anesthetics and regeneration of the damaged muscle fibers. Anesth Analg 59(10):727–736

    CAS  PubMed  Google Scholar 

  36. Brun A (1959) Effect of procaine, carbocain and xylocaine on cutaneous muscle in rabbits and mice. Acta Anaesthesiol Scand 3(2):59–73

    CAS  PubMed  Google Scholar 

  37. Zink W, Graf BM (2004) Local anesthetic myotoxicity. Reg Anesth Pain Med 29(4):333–340

    CAS  PubMed  Google Scholar 

  38. Nouette-Gaulain K, Bringuier S, Canal-Raffin M, Bernard N, Lopez S, Dadure C, Masson F, Mercier J, Sztark F, Rossignol R, Capdevila X (2010) Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle. Can J Anaesth 57(9):836–842. doi:10.1007/s12630-010-9347-8

    PubMed  Google Scholar 

  39. Hogan Q, Dotson R, Erickson S, Kettler R, Hogan K (1994) Local anesthetic myotoxicity: a case and review. Anesthesiology 80(4):942–947

    CAS  PubMed  Google Scholar 

  40. Neuburger M, Breitbarth J, Reisig F, Lang D, Buttner J (2006) Complications and adverse events in continuous peripheral regional anesthesia Results of investigations on 3,491 catheters. Anaesthesist 55(1):33–40. doi:10.1007/s00101-005-0920-4

    CAS  PubMed  Google Scholar 

  41. Selander D (1993) Neurotoxicity of local anesthetics: animal data. Reg Anesth 18(6 Suppl):461–468

    CAS  PubMed  Google Scholar 

  42. Barnet CS, Louis DN, Kohane DS (2005) Tissue injury from tricyclic antidepressants used as local anesthetics. Anesth Analg 101(6):1838–1843. doi:10.1213/01.ANE.0000184129.50312.C1

    CAS  PubMed  Google Scholar 

  43. Estebe JP, Myers RR (2004) Amitriptyline neurotoxicity: dose-related pathology after topical application to rat sciatic nerve. Anesthesiology 100(6):1519–1525

    CAS  PubMed  Google Scholar 

  44. Lim TK, Macleod BA, Ries CR, Schwarz SK (2007) The quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia in animal models in vivo. Anesthesiology 107(2):305–311. doi:10.1097/01.anes.0000270758.77314.b4

    CAS  PubMed  Google Scholar 

  45. Padera RF, Tse JY, Bellas E, Kohane DS (2006) Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity. Muscle Nerve 34(6):747–753. doi:10.1002/mus.20618

    CAS  PubMed  Google Scholar 

  46. Sakura S, Bollen AW, Ciriales R, Drasner K (1995) Local anesthetic neurotoxicity does not result from blockade of voltage-gated sodium channels. Anesth Analg 81(2):338–346

    CAS  PubMed  Google Scholar 

  47. Kohane DS, Lu NT, Gokgol-Kline AC, Shubina M, Kuang Y, Hall S, Strichartz GR, Berde CB (2000) The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo. Reg Anesth Pain Med 25(1):52–59

    CAS  PubMed  Google Scholar 

  48. Colombo G, Langer R, Kohane DS (2004) Effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles at the sciatic nerve. J Biomed Mater Res A 68(4):651–659. doi:10.1002/jbm.a.20074

    PubMed  Google Scholar 

  49. Colombo G, Padera R, Langer R, Kohane DS (2005) Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone. J Biomed Mater Res A 75(2):458–464. doi:10.1002/jbm.a.30443

    PubMed  Google Scholar 

  50. Kohane DS, Langer R (2010) Biocompatibility and drug delivery systems. Chem Sci 1(4):441–446. doi:10.1039/c0sc00203h

    CAS  Google Scholar 

  51. Kohane DS, Tse JY, Yeo Y, Padera R, Shubina M, Langer R (2006) Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum. J Biomed Mater Res A 77(2):351–361. doi:10.1002/jbm.a.30654

    PubMed  Google Scholar 

  52. Leng F, Wan J, Liu W, Tao B, Chen X (2012) Prolongation of epidural analgesia using solid lipid nanoparticles as drug carrier for lidocaine. Reg Anesth Pain Med 37(2):159–165. doi:10.1097/AAP.0b013e31823fc058

    CAS  PubMed  Google Scholar 

  53. De Melo NF, De Araujo DR, Grillo R, Moraes CM, De Matos AP, de Paula E, Rosa AH, Fraceto LF (2012) Benzocaine-loaded polymeric nanocapsules: study of the anesthetic activities. J Pharm Sci 101(3):1157–1165. doi:10.1002/jps.22829

    PubMed  Google Scholar 

  54. Lian T, Ho RJ (2001) Trends and developments in liposome drug delivery systems. J Pharm Sci 90(6):667–680

    CAS  PubMed  Google Scholar 

  55. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4(2):145–160. doi:10.1038/nrd1632

    CAS  PubMed  Google Scholar 

  56. Rose JS, Neal JM, Kopacz DJ (2005) Extended-duration analgesia: update on microspheres and liposomes. Reg Anesth Pain Med 30(3):275–285

    CAS  PubMed  Google Scholar 

  57. de Paula E, Cereda CM, Tofoli GR, Franz-Montan M, Fraceto LF, de Araujo DR (2010) Drug delivery systems for local anesthetics. Recent Pat Drug Deliv Formul 4(1):23–34

    PubMed  Google Scholar 

  58. Boogaerts J, Declercq A, Lafont N, Benameur H, Akodad EM, Dupont JC, Legros FJ (1993) Toxicity of bupivacaine encapsulated into liposomes and injected intravenously: comparison with plain solutions. Anesth Analg 76(3):553–555

    CAS  PubMed  Google Scholar 

  59. Mashimo T, Uchida I, Pak M, Shibata A, Nishimura S, Inagaki Y, Yoshiya I (1992) Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine. Anesth Analg 74(6):827–834

    CAS  PubMed  Google Scholar 

  60. Mura P, Maestrelli F, Gonzalez-Rodriguez ML, Michelacci I, Ghelardini C, Rabasco AM (2007) Development, characterization and in vivo evaluation of benzocaine-loaded liposomes. Eur J Pharm Biopharm 67(1):86–95. doi:10.1016/j.ejpb.2007.01.020

    CAS  PubMed  Google Scholar 

  61. Mowat JJ, Mok MJ, MacLeod BA, Madden TD (1996) Liposomal bupivacaine. Extended duration nerve blockade using large unilamellar vesicles that exhibit a proton gradient. Anesthesiology 85(3):635–643

    CAS  PubMed  Google Scholar 

  62. Madden TD, Harrigan PR, Tai LC, Bally MB, Mayer LD, Redelmeier TE, Loughrey HC, Tilcock CP, Reinish LW, Cullis PR (1990) The accumulation of drugs within large unilamellar vesicles exhibiting a proton gradient: a survey. Chem Phys Lipids 53(1):37–46

    CAS  PubMed  Google Scholar 

  63. Grant GJ, Barenholz Y, Bolotin EM, Bansinath M, Turndorf H, Piskoun B, Davidson EM (2004) A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia. Anesthesiology 101(1):133–137

    CAS  PubMed  Google Scholar 

  64. Grant GJ, Barenholz Y, Piskoun B, Bansinath M, Turndorf H, Bolotin EM (2001) DRV liposomal bupivacaine: preparation, characterization, and in vivo evaluation in mice. Pharm Res 18(3):336–343

    CAS  PubMed  Google Scholar 

  65. Grant GJ, Piskoun B, Bansinath M (2003) Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice. Clin Exp Pharmacol Physiol 30(12):966–968

    CAS  PubMed  Google Scholar 

  66. Grant SA (2002) The Holy Grail: long-acting local anaesthetics and liposomes. Best Pract Res Clin Anaesthesiol 16(2):345–352

    CAS  PubMed  Google Scholar 

  67. Shipton EA (2012) New formulations of local anaesthetics-part I. Anesthesiol Res Pract 2012:546409. doi:10.1155/2012/546409

    PubMed Central  PubMed  Google Scholar 

  68. Smith KJ, McDonald WI (1980) Spontaneous and mechanically evoked activity due to central demyelinating lesion. Nature 286(5769):154–155

    CAS  PubMed  Google Scholar 

  69. Hall SM, Gregson NA (1971) The in vivo and ultrastructural effects of injection of lysophosphatidyl choline into myelinated peripheral nerve fibres of the adult mouse. J Cell Sci 9(3):769–789

    CAS  PubMed  Google Scholar 

  70. Gorfine SR, Onel E, Patou G, Krivokapic ZV (2011) Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum 54(12):1552–1559. doi:10.1097/DCR.0b013e318232d4c1

    PubMed  Google Scholar 

  71. Golf M, Daniels SE, Onel E (2011) A phase 3, randomized, placebo-controlled trial of DepoFoam(R) bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther 28(9):776–788. doi:10.1007/s12325-011-0052-y

    CAS  PubMed  Google Scholar 

  72. Bramlett K, Onel E, Viscusi ER, Jones K (2012) A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee 19(5):530–536. doi:10.1016/j.knee.2011.12.004

    PubMed  Google Scholar 

  73. Smoot JD, Bergese SD, Onel E, Williams HT, Hedden W (2012) The efficacy and safety of DepoFoam bupivacaine in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty: a randomized, double-blind, active-control study. Aesthet Surg J 32(1):69–76. doi:10.1177/1090820X11430831

    PubMed  Google Scholar 

  74. Bragagni M, Maestrelli F, Mennini N, Ghelardini C, Mura P (2010) Liposomal formulations of prilocaine: effect of complexation with hydroxypropyl-ss-cyclodextrin on drug anesthetic efficacy. J Liposome Res 20(4):315–322. doi:10.3109/08982100903544169

    CAS  PubMed  Google Scholar 

  75. Shikanov A, Domb AJ, Weiniger CF (2007) Long acting local anesthetic-polymer formulation to prolong the effect of analgesia. J Control Release 117(1):97–103. doi:10.1016/j.jconrel.2006.10.014

    CAS  PubMed  Google Scholar 

  76. Blanco MD, Bernardo MV, Sastre RL, Olmo R, Muniz E, Teijon JM (2003) Preparation of bupivacaine-loaded poly(epsilon-caprolactone) microspheres by spray drying: drug release studies and biocompatibility. Eur J Pharm Biopharm 55(2):229–236

    CAS  PubMed  Google Scholar 

  77. Kojima T, Nakano M, Juni K, Inoue S, Yoshida Y (1985) Preparation and evaluation in vitro and in vivo of polycarbonate microspheres containing dibucaine. Chem Pharm Bull (Tokyo) 33(11):5119–5125

    CAS  Google Scholar 

  78. Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21(23):2475–2490

    CAS  PubMed  Google Scholar 

  79. Chen PC, Kohane DS, Park YJ, Bartlett RH, Langer R, Yang VC (2004) Injectable microparticle-gel system for prolonged and localized lidocaine release. II. In vivo anesthetic effects. J Biomed Mater Res A 70(3):459–466. doi:10.1002/jbm.a.30101

    PubMed  Google Scholar 

  80. Chen PC, Park YJ, Chang LC, Kohane DS, Bartlett RH, Langer R, Yang VC (2004) Injectable microparticle-gel system for prolonged and localized lidocaine release. I. In vitro characterization. J Biomed Mater Res A 70(3):412–419. doi:10.1002/jbm.a.30086

    PubMed  Google Scholar 

  81. Horie RT, Sakamoto T, Nakagawa T, Tabata Y, Okamura N, Tomiyama N, Tachibana M, Ito J (2010) Sustained delivery of lidocaine into the cochlea using poly lactic/glycolic acid microparticles. Laryngoscope 120(2):377–383. doi:10.1002/lary.20713

    CAS  PubMed  Google Scholar 

  82. Le Corre P, Estebe JP, Clement R, Du Plessis L, Chevanne F, Ecoffey C, Le Verge R (2002) Spray-dryed bupivacaine-loaded microspheres: in vitro evaluation and biopharmaceutics of bupivacaine following brachial plexus administration in sheep. Int J Pharm 238(1–2):191–203

    PubMed  Google Scholar 

  83. Xu Q, Hashimoto M, Dang TT, Hoare T, Kohane DS, Whitesides GM, Langer R, Anderson DG (2009) Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small 5(13):1575–1581. doi:10.1002/smll.200801855

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Wang CF, Pancaro C, Gerner P, Strichartz G (2011) Prolonged suppression of postincisional pain by a slow-release formulation of lidocaine. Anesthesiology 114(1):135–149. doi:10.1097/ALN.0b013e3182001996

    CAS  PubMed  Google Scholar 

  85. Gerner P, Wang CF, Lee BS, Suzuki S, Degirolami U, Gandhi A, Knaack D, Strichartz G (2010) The relationship between functional sciatic nerve block duration and the rate of release of lidocaine from a controlled-release matrix. Anesth Analg 111(1):221–229. doi:10.1213/ANE.0b013e3181dd2690

    CAS  PubMed  Google Scholar 

  86. Tobe M, Obata H, Suto T, Yokoo H, Nakazato Y, Tabata Y, Saito S (2010) Long-term effect of sciatic nerve block with slow-release lidocaine in a rat model of postoperative pain. Anesthesiology 112(6):1473–1481. doi:10.1097/ALN.0b013e3181d4f66f

    CAS  PubMed  Google Scholar 

  87. Blanco MD, Bernardo MV, Gomez C, Muniz E, Teijon JM (1999) Bupivacaine-loaded comatrix formed by albumin microspheres included in a poly(lactide-co-glycolide) film: in vivo biocompatibility and drug release studies. Biomaterials 20(20):1919–1924

    CAS  PubMed  Google Scholar 

  88. Masters DB, Berde CB, Dutta S, Turek T, Langer R (1993) Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia. Pharm Res 10(10):1527–1532

    CAS  PubMed  Google Scholar 

  89. Masters DB, Berde CB, Dutta SK, Griggs CT, Hu D, Kupsky W, Langer R (1993) Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable polymer matrix. Anesthesiology 79(2):340–346

    CAS  PubMed  Google Scholar 

  90. Hersh EV, Maniar M, Green M, Cooper SA (1992) Anesthetic activity of the lipospheres bupivacaine delivery system in the rat. Anesth Prog 39(6):197–200

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Masters DB, Domb AJ (1998) Liposphere local anesthetic timed-release for perineural site application. Pharm Res 15(7):1038–1045

    CAS  PubMed  Google Scholar 

  92. Toongsuwan S, Li LC, Erickson BK, Chang HC (2004) Formulation and characterization of bupivacaine lipospheres. Int J Pharm 280(1–2):57–65. doi:10.1016/j.ijpharm.2004.04.020

    CAS  PubMed  Google Scholar 

  93. Pietkiewicz J, Sznitowska M, Placzek M (2006) The expulsion of lipophilic drugs from the cores of solid lipid microspheres in diluted suspensions and in concentrates. Int J Pharm 310(1–2):64–71. doi:10.1016/j.ijpharm.2005.11.038

    CAS  PubMed  Google Scholar 

  94. Yeo Y, Kohane DS (2008) Polymers in the prevention of peritoneal adhesions. Eur J Pharm Biopharm 68(1):57–66. doi:10.1016/j.ejpb.2007.03.027

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Sivakumaran D, Maitland D, Hoare T (2011) Injectable microgel-hydrogel composites for prolonged small-molecule drug delivery. Biomacromolecules 12(11):4112–4120. doi:10.1021/bm201170h

    CAS  PubMed  Google Scholar 

  96. Bulpitt P, Aeschlimann D (1999) New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. J Biomed Mater Res 47(2):152–169

    CAS  PubMed  Google Scholar 

  97. Paavola A, Yliruusi J, Kajimoto Y, Kalso E, Wahlstrom T, Rosenberg P (1995) Controlled release of lidocaine from injectable gels and efficacy in rat sciatic nerve block. Pharm Res 12(12):1997–2002

    CAS  PubMed  Google Scholar 

  98. Paavola A, Tarkkila P, Xu M, Wahlstrom T, Yliruusi J, Rosenberg P (1998) Controlled release gel of ibuprofen and lidocaine in epidural use–analgesia and systemic absorption in pigs. Pharm Res 15(3):482–487. doi:10.1023/A:1011992702604

    CAS  PubMed  Google Scholar 

  99. Karashima K, Taniguchi M, Nakamura T, Takasaki M, Matsuo K, Irikura M, Irie T (2007) Prolongation of intrathecal and sciatic nerve blocks using a complex of levobupivacaine with maltosyl-beta-cyclodextrin in rats. Anesth Analg 104(5):1121–1128. doi:10.1213/01.ane.0000260309.15034.52, tables of contents

    CAS  PubMed  Google Scholar 

  100. Suzuki R, Arai YC, Hamayasu K, Fujita K, Hara K, Yamaguchi T, Sasaguri S (2009) Complex of branched cyclodextrin and lidocaine prolonged the duration of peripheral nerve block. J Anesth 23(2):295–297. doi:10.1007/s00540-008-0720-5

    PubMed  Google Scholar 

  101. de Araujo DR, Tsuneda SS, Cereda CM, Del GFCF, Prete PS, Fernandes SA, Yokaichiya F, Franco MK, Mazzaro I, Fraceto LF, de FABA, de Paula E (2008) Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex. Eur J Pharm Sci 33(1):60–71. doi:10.1016/j.ejps.2007.09.010

    PubMed  Google Scholar 

  102. Cereda CM, Tofoli GR, Maturana LG, Pierucci A, Nunes LA, Franz-Montan M, de Oliveira AL, Arana S, de Araujo DR, de Paula E (2012) Local neurotoxicity and myotoxicity evaluation of cyclodextrin complexes of bupivacaine and ropivacaine. Anesth Analg 115(5):1234–1241. doi:10.1213/ANE.0b013e318266f3d9

    CAS  PubMed  Google Scholar 

  103. Maestrelli F, Gonzalez-Rodriguez ML, Rabasco AM, Ghelardini C, Mura P (2010) New “drug-in cyclodextrin-in deformable liposomes” formulations to improve the therapeutic efficacy of local anaesthetics. Int J Pharm 395(1–2):222–231. doi:10.1016/j.ijpharm.2010.05.046

    CAS  PubMed  Google Scholar 

  104. Sokolsky-Papkov M, Golovanevski L, Domb AJ, Weiniger CF (2010) Poly(DL:lactic acid-castor oil) 3:7-bupivacaine formulation: reducing burst effect prolongs efficacy in vivo. J Pharm Sci 99(6):2732–2738. doi:10.1002/jps.22025

    CAS  PubMed  Google Scholar 

  105. Vaisman B, Motiei M, Nyska A, Domb AJ (2010) Biocompatibility and safety evaluation of a ricinoleic acid-based poly(ester-anhydride) copolymer after implantation in rats. J Biomed Mater Res A 92(2):419–431. doi:10.1002/jbm.a.32342

    PubMed  Google Scholar 

  106. Soderberg L, Dyhre H, Roth B, Bjorkman S (2006) Ultralong peripheral nerve block by lidocaine:prilocaine 1:1 mixture in a lipid depot formulation: comparison of in vitro, in vivo, and effect kinetics. Anesthesiology 104(1):110–121

    PubMed  Google Scholar 

  107. Dyhre H, Soderberg L, Bjorkman S, Carlsson C (2006) Local anesthetics in lipid-depot formulations–neurotoxicity in relation to duration of effect in a rat model. Reg Anesth Pain Med 31(5):401–408. doi:10.1016/j.rapm.2006.05.008

    CAS  PubMed  Google Scholar 

  108. Lee JW, Lim TH, Park JB (2010) Intradiscal drug delivery system for the treatment of low back pain. J Biomed Mater Res A 92(1):378–385. doi:10.1002/jbm.a.32377

    PubMed  Google Scholar 

  109. Yin QQ, Wu L, Gou ML, Qian ZY, Zhang WS, Liu J (2009) Long-lasting infiltration anaesthesia by lidocaine-loaded biodegradable nanoparticles in hydrogel in rats. Acta Anaesthesiol Scand 53(9):1207–1213. doi:10.1111/j.1399-6576.2009.02030.x

    CAS  PubMed  Google Scholar 

  110. Cohen R, Kanaan H, Grant GJ, Barenholz Y (2012) Prolonged analgesia from Bupisome and Bupigel formulations: from design and fabrication to improved stability. J Control Release 160(2):346–352. doi:10.1016/j.jconrel.2011.12.030

    CAS  PubMed  Google Scholar 

  111. Verron E, Gauthier O, Janvier P, Le Guen H, Holopherne D, Cavagna R, Bouler JM (2010) Analgesic properties of calcium phosphate apatite loaded with bupivacaine on postoperative pain. J Biomed Mater Res B Appl Biomater 94(1):89–96. doi:10.1002/jbm.b.31628

    PubMed  Google Scholar 

  112. Radin S, Campbell JT, Ducheyne P, Cuckler JM (1997) Calcium phosphate ceramic coatings as carriers of vancomycin. Biomaterials 18(11):777–782

    CAS  PubMed  Google Scholar 

  113. Hamanishi C, Kitamoto K, Tanaka S, Otsuka M, Doi Y, Kitahashi T (1996) A self-setting TTCP-DCPD apatite cement for release of vancomycin. J Biomed Mater Res 33(3):139–143. doi:10.1002/(SICI)1097-4636(199623)33:3<139::AID-JBM3>3.0.CO;2-R

    CAS  PubMed  Google Scholar 

  114. Tiwary AK, Sapra B, Jain S (2007) Innovations in transdermal drug delivery: formulations and techniques. Recent Pat Drug Deliv Formul 1(1):23–36

    CAS  PubMed  Google Scholar 

  115. Sawyer J, Febbraro S, Masud S, Ashburn MA, Campbell JC (2009) Heated lidocaine/tetracaine patch (Synera, Rapydan) compared with lidocaine/prilocaine cream (EMLA) for topical anaesthesia before vascular access. Br J Anaesth 102(2):210–215. doi:10.1093/bja/aen364

    CAS  PubMed  Google Scholar 

  116. Cho CW, Choi JS, Shin SC (2011) Enhanced local anesthetic action of mepivacaine from the bioadhesive gels. Pak J Pharm Sci 24(1):87–93

    CAS  PubMed  Google Scholar 

  117. He CX, He ZG, Gao JQ (2010) Microemulsions as drug delivery systems to improve the solubility and the bioavailability of poorly water-soluble drugs. Expert Opin Drug Deliv 7(4):445–460. doi:10.1517/17425241003596337

    CAS  PubMed  Google Scholar 

  118. Yuan JS, Yip A, Nguyen N, Chu J, Wen XY, Acosta EJ (2010) Effect of surfactant concentration on transdermal lidocaine delivery with linker microemulsions. Int J Pharm 392(1–2):274–284. doi:10.1016/j.ijpharm.2010.03.051

    CAS  PubMed  Google Scholar 

  119. Lafont ND, Boogaerts JG, Legros FJ (1994) Use of liposome-associated bupivacaine for the management of a chronic pain syndrome. Anesth Analg 79(4):818

    CAS  PubMed  Google Scholar 

  120. Lafont ND, Legros FJ, Boogaerts JG (1996) Use of liposome-associated bupivacaine in a cancer pain syndrome. Anaesthesia 51(6):578–579

    CAS  PubMed  Google Scholar 

  121. Boogaerts JG, Lafont ND, Declercq AG, Luo HC, Gravet ET, Bianchi JA, Legros FJ (1994) Epidural administration of liposome-associated bupivacaine for the management of postsurgical pain: a first study. J Clin Anesth 6(4):315–320

    CAS  PubMed  Google Scholar 

  122. Holte K, Werner MU, Lacouture PG, Kehlet H (2002) Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers. Anesthesiology 96(6):1331–1335

    CAS  PubMed  Google Scholar 

  123. Pedersen JL, Lilleso J, Hammer NA, Werner MU, Holte K, Lacouture PG, Kehlet H (2004) Bupivacaine in microcapsules prolongs analgesia after subcutaneous infiltration in humans: a dose-finding study. Anesth Analg 99(3):912–918. doi:10.1213/01.ANE.0000143791.77608.0B, table of contents

    CAS  PubMed  Google Scholar 

  124. Kopacz DJ, Lacouture PG, Wu D, Nandy P, Swanton R, Landau C (2003) The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostal blockade (T9 to T11) in healthy volunteers. Anesth Analg 96(2):576–582, table of contents

    CAS  PubMed  Google Scholar 

  125. Richard BM, Ott LR, Haan D, Brubaker AN, Cole PI, Nelson KG, Ross PE, Rebelatto MC, Newton PE (2011) The safety and tolerability evaluation of DepoFoam bupivacaine (bupivacaine extended-release liposome injection) administered by incision wound infiltration in rabbits and dogs. Expert Opin Investig Drugs 20(10):1327–1341. doi:10.1517/13543784.2011.611499

    CAS  PubMed  Google Scholar 

  126. Wakiyama N, Juni K, Nakano M (1982) Preparation and evaluation in vitro and in vivo of polylactic acid microspheres containing dibucaine. Chem Pharm Bull (Tokyo) 30(10):3719–3727

    CAS  Google Scholar 

  127. Rodriguez-Navarro AJ, Lagos M, Figueroa C, Garcia C, Recabal P, Silva P, Iglesias V, Lagos N (2009) Potentiation of local anesthetic activity of neosaxitoxin with bupivacaine or epinephrine: development of a long-acting pain blocker. Neurotox Res 16(4):408–415. doi:10.1007/s12640-009-9092-3

    CAS  PubMed  Google Scholar 

  128. Timko BP, Dvir T, Kohane DS (2010) Remotely triggerable drug delivery systems. Adv Mater 22(44):4925–4943. doi:10.1002/adma.201002072

    CAS  PubMed  Google Scholar 

  129. Richard BM, Rickert DE, Newton PE, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG (2011) Safety evaluation of exparel (DepoFoam bupivacaine) administered by repeated subcutaneous injection in rabbits and dogs: Species comparison. J drug deliv 2011:467429. doi:10.115/2011/467429

    CAS  PubMed  Google Scholar 

  130. Richard BM, Newton P, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG (2012) The safety of Exparel® (bupivacaine liposomal injectable suspension) administered by peripheral nerve block in rabbits and dogs. J Drug deliv 2012:962101. doi:10.1155/2012/962101

    CAS  PubMed  Google Scholar 

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McAlvin, J.B., Kohane, D.S. (2014). Prolonged Duration Local Anesthesia. In: Domb, A., Khan, W. (eds) Focal Controlled Drug Delivery. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-9434-8_28

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