Development and characterization of PLGA-Bupivacaine and PLGA-S75
R25 Bupivacaine (Novabupi®) biodegradable implants for postoperative pain
DOI:
https://doi.org/10.1590/s2175-97902022e21310Palavras-chave:
Postoperative Pain, Bupivacaine, Novabupi®, Biodegradable Implants, PLGAResumo
In the hospital environment, postoperative pain is a common occurrence that impairs patient recovery and rehabilitation and lengthens hospitalization time. Racemic bupivacaine hydrochloride (CBV) and Novabupi® (NBV) (S (-) 75% R (+) 25% bupivacaine hydrochloride) are two examples of local anesthetics used in pain management, the latter being an alternative with less deleterious effects. In the present study, biodegradable implants were developed using Poly(L-lactide-co-glycolide) through a hot molding technique, evaluating their physicochemical properties and their in vitro drug release. Different proportions of drugs and polymer were tested, and the proportion of 25%:75% was the most stable for molding the implants. Thermal and spectrometric analyses were performed, and they revealed no unwanted chemical interactions between drugs and polymer. They also confirmed that heating and freeze-drying used for manufacturing did not interfere with stability. The in vitro release results revealed drugs sustained release, reaching 64% for NBV-PLGA and 52% for CBV-PLGA up to 30 days. The drug release mechanism was confirmed by microscopy, which involved pores formation and polymeric erosion, visualized in the first 72 h of the in vitro release test. These findings suggest that the developed implants are interesting alternatives to control postoperative pain efficiently.
Downloads
Referências
Alijanipour P, Tan TL, Matthews CN, Viola JR, Purtill JJ, Rothman RH, et al. Periarticular injection of liposomal bupivacaine offers no benefit over standard bupivacaine in total knee arthroplasty: A prospective, randomized, controlled trial. J Arthroplasty. 2017;32(2):628-34. https://doi.org/10.1016/j.arth.2016.07.023.
» https://doi.org/https://doi.org/10.1016/j.arth.2016.07.023
Anwer MK, Al-Mansoor MA, Jamil S, Al-Shdefat R, Ansari MN, Shakeel F. Development and evaluation of PLGA polymer based nanoparticles of quercetin. Int J Biol Macromol. 2016;92:213-9. https://doi.org/10.1016/j.ijbiomac.2016.07.002.
» https://doi.org/https://doi.org/10.1016/j.ijbiomac.2016.07.002
Couceiro TC de M, Valença MM, Lima LC, de Menezes TC, Raposo MCF. Prevalence and influence of gender, age, and type of surgery on postoperative pain. Braz J Anesthesiol. 2009;59(3):314-20. https://doi.org/10.1590/s0034-70942009000300006.
» https://doi.org/https://doi.org/10.1590/s0034-70942009000300006
Cox CR, Checketts MR, Mackenzie N, Scott NB, Bannister J. Comparison of S(-)-bupivacaine with racemic (RS)-bupivacaine in supraclavicular brachial plexus block. Br J Anaesth. 1998;80(5):594-8. https://doi.org/10.1093/bja/80.5.594.
» https://doi.org/https://doi.org/10.1093/bja/80.5.594
Elmallah RK, Chughtai M, Khlopas A, Newman JM, Stearns KL, Roche M, et al. Pain Control in Total Knee Arthroplasty. J Knee Surg. 2018;31(6):504-13. https://doi.org/10.1055/s-0037-1604152.
» https://doi.org/https://doi.org/10.1055/s-0037-1604152
Francisco L, Bastos S, Vago JP, Caux TR, Costa BL, Godin AM, et al. Delay of neuropathic pain sensitization after application of dexamethasone-loaded implant in sciatic nerve-injured rats. Braz J Pharm Sci. 2019;55:e18112.
Fredenberg S, Wahlgren M, Reslow M, Axelsson A. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems - A review. Int J Pharm. 2011;415(1-2):34-52. https://doi.org/10.1016/j.ijpharm.2011.05.049.
» https://doi.org/https://doi.org/10.1016/j.ijpharm.2011.05.049
Grillo R, de Melo N, de Araújo D, de Paula E, Rosa A, Fraceto L. Polymeric alginate nanoparticles containing the local anesthetic bupivacaine. J. Drug Target. 2010;18(9):688-699.
Hamaji A, de Rezende MR, Mattar R, Vieira JE, Auler JOC. Estudo comparativo entre bupivacaína (S75-R25) e ropivacaína para avaliar a segurança cardiovascular em loqueio do plexo braquial. Rev Bras Anestesiol. 2013;63(4):322-6. https://doi.org/10.1016/j.bjan.2012.06.001.
» https://doi.org/https://doi.org/10.1016/j.bjan.2012.06.001
Hussain N, Brull R, Sheehy B, Essandoh MK, Stahl DL, Weaver TE, et al. Perineural liposomal bupivacaine is not superior to nonliposomal bupivacaine for peripheral nerve block analgesia. Anesthesiology.2021;134(2):147-64. https://doi.org/10.1097/aln.0000000000003651.
» https://doi.org/https://doi.org/10.1097/aln.0000000000003651
Jahangiri A, Davaran S, Fayyazi B, Tanhaei A, Payab S, Adibkia K. Application of electrospraying as a one-step method for the fabrication of triamcinolone acetonide-PLGA nanofibers and nanobeads. Colloids Surf, B. 2014;123:219-24. https://doi.org/10.1016/j.colsurfb.2014.09.019.
» https://doi.org/https://doi.org/10.1016/j.colsurfb.2014.09.019
Kim S, Hyeon B, Koo H, Bin Y. Poly (lactic-co-glycolic acid) microparticles in fibrin glue for local, sustained delivery of bupivacaine. J Ind Eng Chem. 2019;75:86-92. https://doi.org/10.1016/j.jiec.2019.02.028.
» https://doi.org/https://doi.org/10.1016/j.jiec.2019.02.028
Kranz H, Yilmaz E, Brazeau GA, Bodmeier R. In Vitro and In Vivo Drug Release from a Novel In Situ Forming Drug Delivery System. Pharm Res. 2008;25. (6):1347-54. https://doi.org/10.1007/s11095-007-9478-y.
» https://doi.org/https://doi.org/10.1007/s11095-007-9478-y
Lamplot JD, Wagner ER, Manning DW. Multimodal pain management in total knee arthroplasty. a prospective randomized controlled trial. J Arthroplasty . 2014;29(3):329-34. https://doi.org/10.1016/j.arth.2013.06.005.
» https://doi.org/https://doi.org/10.1016/j.arth.2013.06.005
Lee SS, Hughes P, Ross AD, Robinson MR. Biodegradable implants for sustained drug release in the eye. Pharm Res . 2010;27(10):2043-53. https://doi.org/10.1007/s11095-010-0159-x.
» https://doi.org/https://doi.org/10.1007/s11095-010-0159-x
Leiman D, Niebler G, Minkowitz HS. Pharmacokinetics and Safety of INL-001 (Bupivacaine HCl) Implants Compared with Bupivacaine HCl Infiltration After Open Unilateral Inguinal Hernioplasty. Adv Ther. 2021;38(1):691-706. https://doi.org/10.1007/s12325-020-01565-x.
» https://doi.org/https://doi.org/10.1007/s12325-020-01565-x
Lopes B, Resende R De, Rodrigues M, Paiva B, Serakides R, Matos M De, et al. Sirolimus-loaded biodegradable implants induce long lasting anti- in fl ammatory and antiangiogenic effects. J Drug Delivery Sci Technol. 2018;44:373-9. https://doi.org/10.1016/j.jddst.2018.01.018.
» https://doi.org/https://doi.org/10.1016/j.jddst.2018.01.018
Lorincz A, Mihály J, Németh C, Wacha A, Bóta A. Effects of ursolic acid on the structural and morphological behaviours of dipalmitoyl lecithin vesicles. Biochim Biophys Acta, Biomembranes. 2015;1848(5):1092-8. https://doi.org/10.1016/j.bbamem.2015.01.010.
» https://doi.org/https://doi.org/10.1016/j.bbamem.2015.01.010
Martins ML, Eckert J, Jacobsen H, dos Santos EC, Ignazzi R, de Araujo DR, et al. Raman and Infrared spectroscopies and X-ray diffraction data on bupivacaine and ropivacaine complexed with 2-hydroxypropyl−β−cyclodextrin. Data Brief. 2017;15:25-9. https://doi.org/10.1016/j.dib.2017.08.053.
» https://doi.org/https://doi.org/10.1016/j.dib.2017.08.053
Mir M, Ahmed N, Rehman A ur. Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf , B. 2017;159:217-31. https://doi.org/10.1016/j. colsurfb.2017.07.038.
» https://doi.org/https://doi.org/10.1016/j. colsurfb.2017.07.038
Nelson M, Reens A, Reda L, Lee D. Profound Prolonged Bradycardia and Hypotension after Interscalene Brachial Plexus Block with Bupivacaine. J Emerg Med 2018;54(3):e41-43. https://doi.org/10.1016/j.jemermed.2017.12.004.
» https://doi.org/https://doi.org/10.1016/j.jemermed.2017.12.004
Pereira RJ, Munechika M, Sakata RK. Pain management after outpatient surgical procedure. Rev Dor. 2013;14(1):61-7.
Sadeghi-avalshahr A, Nokhasteh S, Molavi AM. Synthesis and characterization of collagen/PLGA biodegradable skin scaffold fibers. Regen Biomater. 2017;4(5):309-14. https://doi.org/10.1093/rb/rbx026.
» https://doi.org/https://doi.org/10.1093/rb/rbx026
Sendil D, Bonney IM, Carr DB, Lipkowski AW, Wise DL, Hasirci V. Antinociceptive effects of hydromorphone, bupivacaine and biphalin released from PLGA polymer after intrathecal implantation in rats. Biomaterials. 2003;24(11):1969-76. https://doi.org/10.1016/S0142-9612(02)00567-7.
» https://doi.org/https://doi.org/10.1016/S0142-9612(02)00567-7
Soares DCF, de Paula Oliveira DC, Barcelos LS, Barbosa AS, Vieira LC, Townsend DM, et al. Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications. Biomed Pharmacother. 2017;92:394-402. https://doi.org/10.1016/j.biopha.2017.05.093.
» https://doi.org/https://doi.org/10.1016/j.biopha.2017.05.093
Sykuła-Zając A, Łodyga-Chruścińska E, Pałecz B, Dinnebier RE, Griesser UJ, Niederwanger V. Thermal and X-ray analysis of racemic bupivacaine hydrochloride. J Therm Anal Calorim. 2011;105:1031-6. https://doi.org/10.1007/s10973-011-1425-9.
» https://doi.org/https://doi.org/10.1007/s10973-011-1425-9
Taraballi F, Minardi S, Corradetti B, Yazdi I, Balliano M, Van Eps J, et al. Potential avoidance of adverse analgesic effects using a biologically “smart” hydrogel capable of controlled bupivacaine release. J Pharm Sci. 2014;103(11):3724-3723. https://doi.org/10.1002/jps.24190
» https://doi.org/https://doi.org/10.1002/jps.24190
Velanovich V, Rider P, Deck K, Minkowitz HS, Leiman D, Jones N, et al. Safety and Efficacy of Bupivacaine HCl Collagen-Matrix Implant (INL-001) in Open Inguinal Hernia Repair: Results from Two Randomized Controlled Trials. Adv Ther . 2019;36(1):200-16. https://doi.org/10.1007/s12325-018-0836-4.
» https://doi.org/https://doi.org/10.1007/s12325-018-0836-4
Wang B, Wang S, Zhang Q, Deng Y, Li X, Peng L, et al. Recent advances in polymer-based drug delivery systems for local anesthetics. Acta Biomater. 2019;96:55-67. https://doi.org/10.1016/j.actbio.2019.05.044.
» https://doi.org/https://doi.org/10.1016/j.actbio.2019.05.044
Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med. 2010;35(2):188-93. https://doi.org/10.1097/AAP.0b013e3181d246c3.
» https://doi.org/https://doi.org/10.1097/AAP.0b013e3181d246c3
Wu CL, Raja SN. Treatment of acute postoperative pain. Lancet. 2011;377(9784):2215-25. https://doi.org/10.1016/S0140-6736(11)60245-6.
» https://doi.org/https://doi.org/10.1016/S0140-6736(11)60245-6
Zhang H, Lu Y, Zhang G, Gao S, Sun D, Zhong Y. Bupivacaine-loaded biodegradable poly(lactic-co-glycolic) acid microspheres. Optimization of the drug incorporation into the polymer matrix and modelling of drug release. Int J Pharm . 2008;351(1-2):244-249.
Zhang J, Shi K, Jia H. Ketamine and bupivacaine attenuate post-operative pain following total knee arthroplasty: A randomized clinical trial. Exp Ther Med. 2018;15(6):5537-43. https://doi.org/10.3892/etm.2018.6104.
Downloads
Publicado
Edição
Seção
Licença
Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.
