Permeability and in vivo distribution of poly(Ɛ-caprolactone) nanoparticles loaded with zidovudine
Source abstract
Abstract
Zidovudine (AZT) is one of first choice drugs for the treatment of acquired immunodeficiency syndrome (AIDS). Despite its efficacy to control virus replication, the extent of adverse effects and the therapeutic regimen are directly related to patients’ non-compliance. In this work, we evaluated the permeability and in vivo distribution of AZT incorporated into poly(Ɛ-caprolactone), PCL, nanoparticles (AZT-NP) aiming to reduce the normally observed side effects and increase the drug bioavailability. AZT-NP were obtained by interfacial deposition of preformed polymer. The mean diameter of the nanoparticles was 283.4 nm ± 17.0 with a polydispersity index of 0.232 ± 0.073. The nanoparticles presented a zeta potential of − 32.4 mV ± 3.3, entrapment rate of 53.11% ± 9.25, and were stable for at least 7 days. The drug and the polymer showed no incompatibility in thermal analysis. The permeability of AZT across Caco-2 cells was 22-fold higher for AZT-NP compared to the drug solution. The nanoparticles were able to release AZT in vivo after oral administration in mice, and the plasma levels of labeled AZT-NP were higher and more constant when compared to free labeled AZT. Thus, AZT-NP demonstrated superior performance compared to the drug solution in vivo and in vitro, showing the potential of this system for the treatment of AIDS.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: HIV/AIDS Research and Interventions · HIV/AIDS drug development and treatment · Pneumocystis jirovecii pneumonia detection and treatment
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (74)
Show source-provided references
1. Ait Slimane T, Hoekstra D (2002) Sphingolipid trafficking and protein sorting in epithelial cells. FEBS Lett 529(1):54–5910.1016/S0014-5793(02)03183-6 ↗
2. Araújo AAS, Storpirtis S, Mercuri LP, Carvalho FMS, Dos Santos Filho M, Matos JR (2003) Thermal analysis of the antiretroviral zidovudine (AZT) and evaluation of the compatibility with excipients used in solid dosage forms. Int J Pharm 260(2):303–31410.1016/S0378-5173(03)00288-6 ↗
3. Awasthi VD, Garcia D, Goins BA, Phillips WT (2003) Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits. Int J Pharm 253(1–2):121–13210.1016/S0378-5173(02)00703-2 ↗
4. Badowski ME, Pérez SE, Biagi M, Littler JA (2016) New antiretroviral treatment for HIV. Infect Dis Ther 5(3):329–35210.1007/s40121-016-0126-x ↗
5. Barbanti SH, Zavaglia CAC, Duek EAR (2006) Accelerated degradation of poly(ε-caprolactone) and poly(D,L-lactic acid-co-glycolic acid) scaffolds in alkaline medium. Polímeros 16(2):141–14810.1590/S0104-14282006000200015 ↗
6. Binaschi M, Supino R, Gambetta RA, Giaccone G, Prosperi E, Capranico G, Catalog I, Zunino F (1995) MRP gene overexpression in a human doxorubicin-resistant SCLC cell line: alterations in cellular pharmacokinetics and in pattern of cross-resistance. Int J Cancer 62(1):84–8910.1002/ijc.2910620116 ↗
7. Blum MR, Liao SHT, Good SS, de Miranda P (1988) Pharmacokinetics and bioavailability of zidovudine in human. Am J Med 85(2A):189–194
8. Celia C, Trapasso E, Cosco D, Paolino D, Fresta M (2009) Turbiscan Lab® expert analysis of the stability of ethosomes® and ultradeformable liposomes containing a bilayer fluidizing agent. Colloids Surf B: Biointerfaces 72(1):155–16010.1016/j.colsurfb.2009.03.007 ↗
9. Chai GH, Xu Y, Chen SQ, Cheng B, Hu FQ, You J, du YZ, Yuan H (2016) Transport mechanisms of solid lipid nanoparticles across Caco-2 cell monolayers and their related cytotoxicology. ACS Appl Mater Interfaces 8(9):5929–594010.1021/acsami.6b00821 ↗
10. Cho EJ, Holback H, Liu KC, Abouelmagd SA, Park J, Yeo Y (2013) Nanoparticle characterization: state of the art, challenges, and emerging technologies. Mol Pharm 10(6):2093–211010.1021/mp300697h ↗
11. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR, HPTN 052 Study Team (2011) Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365(6):493–50510.1056/NEJMoa1105243 ↗
12. Collins JM, Unadkat JD (1989) Clinical pharmacokinetics of zidovudine: an overview of current data. Clin Pharmacokinet 17(1):1–910.2165/00003088-198917010-00001 ↗
13. Dalpiaz A, Contado C, Mari L, Perrone D, Pavan B, Paganetto G et al (2013) Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid. Drug Deliv 7544:1–12
14. Dalpiaz A, Fogagnolo M, Ferraro L, Capuzzo A, Pavan B, Rassu G et al (2015) Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries. Antiviral Res 123:146–15710.1016/j.antiviral.2015.09.013 ↗
15. Dalpiaz A, Paganetto G, Pavan B, Fogagnolo M, Medici A, Beggiato S et al (2012) Zidovudine and ursodeoxycholic acid conjugation: design of a new prodrug potentially able to bypass the active efflux transport systems of the central nervous system. Mol Pharm 9:957–96810.1021/mp200565g ↗
16. Dash TK, Konkimalla VB (2012) Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release 158(1):15–3310.1016/j.jconrel.2011.09.064 ↗
17. De Barros ALB, Das Graças Mota L, Coelho MMA, Corrêa NC, De Góes AM, Oliveira MC et al (2015) Bombesin encapsulated in long-circulating pH-sensitive liposomes as a radiotracer for breast tumor identification. J Biomed Nanotechnol 11(2):342–35010.1166/jbn.2015.1910 ↗
18. Driscoll DF (2006) Lipid injectable emulsions: pharmacopeial and safety issues. Pharm Res 23(9):1959–196910.1007/s11095-006-9092-4 ↗
19. Dubernet C (1995) Thermoanalysis of microspheres. Thermochim Acta 24:259–26910.1016/0040-6031(94)01947-F ↗
20. Duek EAR, Zavaglia CAC, Belangero WD (1999) In vitro study of poly (lactic acid) pin degradation. Polymer 40(23):6465–647310.1016/S0032-3861(98)00846-5 ↗
21. Espuelas MS, Legrand P, Irache JM, Gamazo C, Orecchioni AM, Devissaguet JP, Ygartua P (1997) Poly(ε-caprolactone) nanospheres as an alternative way to reduce amphotericin-B toxicity. Int J Pharm 158(1):19–2710.1016/S0378-5173(97)00194-4 ↗
22. Feng S, Huang G (2001) Effects of emulsifiers on the controlled release of paclitaxel (Taxol®) from nanospheres of biodegradable polymers. J Control Release 71(1):53–6910.1016/S0168-3659(00)00364-3 ↗
23. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55(1):1–410.1016/0378-5173(89)90281-0 ↗
24. Fischl MA, Parker CB, Pettinelli C (1990) A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. N Engl J Med 323(15):1009–101410.1056/NEJM199010113231501 ↗
25. Gajbhiye V, Ganesh N, Barve J, Jain NK (2013) Synthesis, characterization and targeting potential of zidovudine loaded sialic acid conjugated-mannosylated poly(propyleneimine) dendrimers. Eur J Pharm Sci 48(4–5):668–67910.1016/j.ejps.2012.12.027 ↗
26. Gao Y, Kraft JC, Yu D, Ho RJY (2018) Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy. Eur J Pharm Biopharm. https://doi.org/10.1016/j.ejpb.2018.04.01410.1016/j.ejpb.2018.04.014 ↗
27. Gari S, Doig-Acuña C, Smail T, Malungo JR, Martin-Hilber A, Merten S (2013) Access to HIV/AIDS care: a systematic review of socio-cultural determinants in low and high income countries. BMC Health Serv Res 13:19810.1186/1472-6963-13-198 ↗
28. Giacalone G, Bochot A, Fattal E, Hillaireau H (2013) Drug-induced nanocarrier assembly as a strategy for the cellular delivery of nucleotides and nucleotide analogues. Biomacromolecules 14(3):737–74210.1021/bm301832v ↗
29. Gomes MJ, Das Neves J, Sarmento B (2014) Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system. Int J Nanomedicine 9(1):1757–1769
30. Gunaseelan S, Gunaseelan K, Deshmukh M, Zhang X, Sinko PJ (2010) Surface modifications of nanocarriers for effective intracellular delivery of anti-HIV drugs. Adv Drug Deliv Rev 62(4–5):518–53110.1016/j.addr.2009.11.021 ↗
31. He B, Lin P, Jia Z, Du W, Qu W, Yuan L et al (2013) The transport mechanisms of polymer nanoparticles in Caco-2 epithelial cells. Biomaterials 34(25):6082–609810.1016/j.biomaterials.2013.04.053 ↗
32. Hillaireau H, Le Doan T, Besnard M, Chacun H, Janin J, Couvreur P (2006) Encapsulation of antiviral nucleotide analogues azidothymidine-triphosphate and cidofovir in poly(iso-butylcyanoacrylate) nanocapsules. Int J Pharm 324(1):37–4210.1016/j.ijpharm.2006.07.006 ↗
33. Hu L, Tang X, Cui F (2004) Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol 56(12):1527–153510.1211/0022357044959 ↗
34. Jorajuria S, Dereuddre-Bosquet N, Becher F, Martin S, Porcheray F, Garrigues A, Mabondzo A, Benech H, Grassi J, Orlowski S, Dormont D, Clayette P (2004) ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages. Antivir Ther 9(4):519–52810.1177/135965350400900403 ↗
35. Joshi SA, Chavhan SS, Sawant KK (2010) Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm 76(2):189–19910.1016/j.ejpb.2010.07.007 ↗
36. Joshy KS, George A, Jose J, Kalarikkal N, Pothen LA, Thomas S (2017) Novel dendritic structure of alginate hybrid nanoparticles for effective anti-viral drug delivery. Int J Biol Macromol 103:1265–127510.1016/j.ijbiomac.2017.05.094 ↗
37. Kumar A, Sawant K (2013) Encapsulation of exemestane in polycaprolactone nanoparticles: optimization, characterization, and release kinetics. Cancer Nanotechnol 4(4–5):57–7110.1007/s12645-013-0037-4 ↗
38. Kumar P, Lakshmi YS, Bhaskar C, Golla K, Kondapi AK (2015) Improved safety, bioavailability and pharmacokinetics of zidovudine through lactoferrin nanoparticles during oral administration in rats. PLoS One 10(10):1–18
39. Lande MB, Priver NA, Zeidel ML (1994) Determinants of apical membrane permeabilities of barrier epithelia. Am J Phys 267(2 Pt 1):367–37410.1152/ajpcell.1994.267.2.C367 ↗
40. Lee CM, Jeong HJ, Kim DW, Sohn MH, Lim ST (2012) The effect of fluorination of zinc oxide nanoparticles on evaluation of their biodistribution after oral administration. Nanotechnology 23(20):20510210.1088/0957-4484/23/20/205102 ↗
41. Lince F, Marchisio DL, Barresi AA (2008) Strategies to control the particle size distribution of poly-ε-caprolactone nanoparticles for pharmaceutical applications. J Colloid Interface Sci 322(2):505–51510.1016/j.jcis.2008.03.033 ↗
42. Lu Z, Mao C, Meng M, Liu S, Tian Y, Yu L, Sun B, Li CM (2014) Fabrication of CeO2 nanoparticle-modified silk for UV protection and antibacterial applications. J Colloid Interface Sci 435:8–1410.1016/j.jcis.2014.08.015 ↗
43. Mainardes RM, Urban MC, Cinto PO, Chaud MV, Evangelista RC, Gremião MP (2006) Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery. Curr Drug Deliv 3(3):275–28510.2174/156720106777731019 ↗
44. Mainardes RM, Gremião MP, Brunetti IL, da Fonseca LM, Khalil NM (2009) Zidovudine-loaded PLA and PLA–PEG blend nanoparticles: influence of polymer type on phagocytic uptake by polymorphonuclear cells. J Pharm Sci 98(1):257–26710.1002/jps.21406 ↗
45. Mane V, Muro S (2012) Biodistribution and endocytosis of ICAM-1-targeting antibodies versus nanocarriers in the gastrointestinal tract in mice. Int J Nanomedicine 7:4223–4237
46. Malikmammadov E, Tanir TE, Kiziltay A, Hasirci V, Hasirci N (2018) PCL and PCL-based materials in biomedical applications. J Biomater Sci Polym Ed 29(7–9):863–89310.1080/09205063.2017.1394711 ↗
47. Moore KHP, Raasch RH, Brouwer KLR, Opheim K, Cheeseman SH, Eyster E et al (1995) Pharmacokinetics and bioavailability of zidovudine and its glucuronidated metabolite in patients with human immunodeficiency virus infection and hepatic disease (AIDS Clinical Trials Group Protocol 062). Antimicrob Agents Chemother 39(12):2732–273710.1128/AAC.39.12.2732 ↗
48. Mora-Huertas CE, Fessi H, Elaissari A (2010) Polymer-based nanocapsules for drug delivery. Int J Pharm 385(1–2):113–14210.1016/j.ijpharm.2009.10.018 ↗
49. Palumbo PJ, Fogel JM, Hudelson SE, Wilson EA, Hart S, Hovind L et al (2017) HIV drug resistance in adults receiving early versus delayed antiretroviral therapy: Hptn 052. J Acquir Immune Defic Syndr 77(5):484–49110.1097/QAI.0000000000001623 ↗
50. Perloff ES, Duan SX, Skolnik PR, Greenblatt DJ, Von Moltke LL (2005) Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos 33(6):764–77010.1124/dmd.104.002931 ↗
51. Petri N, Tannergren C, Rungstad D, Lennernas H (2004) Transport characteristics of fexofenadine in the Caco-2 cell model. Pharm Res 21(8):1398–140410.1023/B:PHAM.0000036913.90332.b1 ↗
52. Pople PV, Singh KK (2013) Development and evaluation of colloidal modified nanolipid carrier: application to topical delivery of tacrolimus. Part II—in vivo assessment, drug targeting, efficacy, and safety in treatment for atopic dermatitis. Eur J Pharm Biopharm 84(1):72–8310.1016/j.ejpb.2012.11.026 ↗
53. Pople PV, Singh KK (2011) Development and evaluation of colloidal modified nanolipid carrier: application to topical delivery of tacrolimus. Eur J Pharm Biopharm 79:82–9410.1016/j.ejpb.2011.02.016 ↗
54. Quevedo MA, Nieto LE, Briñón MC (2011) P-glycoprotein limits the absorption of the anti-HIV drug zidovudine through rat intestinal segments. Eur J Pharm Sci 43(3):151–15910.1016/j.ejps.2011.04.007 ↗
55. Rachlis A, Fanning MM (1993) Zidovudine toxicity. Clinical features and management. Drug Saf 8(4):312–32010.2165/00002018-199308040-00005 ↗
56. Richman DD, Fischl MA, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, Leedom JM, Groopman JE, Mildvan D, Hirsch MS, Jackson GG, Durack DT, Nusinoff-Lehrman S, The AZT Collaborative Working Group (1987) The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 317(4):192–19710.1056/NEJM198707233170402 ↗
57. Rodriguez-Emmenegger C, Jäger A, Jäger E, Stepanek P, Alles AB, Guterres SS et al (2011) Polymeric nanocapsules ultra stable in complex biological media. Colloids Surf B: Biointerfaces 83(2):3768110.1016/j.colsurfb.2010.12.013 ↗
58. Saiyed ZM, Gandhi NH, Nair MPN (2009) AZT 5′-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells. J Neuro-Oncol 15(4):343–347
59. Saravanan M, Asmalash T, Gebrekidan A, Gebreegziabiher D, Araya T, Hilekiros H, Barabadi H, Ramanathan K (2018) Nano-medicine as a newly emerging approach to combat human immunodeficiency virus (HIV). Pharm Nanotechnol 6:17–2710.2174/2211738506666180209095710 ↗
60. Shamsipur M, Pourmortazavi SM, Beigi AAM, Heydari R, Khatibi M (2013) Thermal stability and decomposition kinetic studies of acyclovir and zidovudine drug compounds. AAPS Pharm Sci Technol 14(1):287–29310.1208/s12249-012-9916-y ↗
61. Shiraki N, Hamada A, Yasuda K, Fujii J, Arimori K, Nakano M (2000) Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoprotein. Biol Pharm Bull 23(12):1528–153110.1248/bpb.23.1528 ↗
62. Silva JO, Fernandes RS, Lopes SCA, Cardoso VN, Leite EA, Cassali GD, Marzola MC, Rubello D, Oliveira MC, de Barros ALB (2016) pH-sensitive, long-circulating liposomes as an alternative tool to deliver doxorubicin into tumors: a feasibility animal study. Mol Imaging Biol 18(6):898–90410.1007/s11307-016-0964-7 ↗
63. Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J (2007) Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol 73(10):1573–158110.1016/j.bcp.2007.01.027 ↗
64. Tamir Z, Alemu J, Tsegaye A (2018a) Anemia among HIV infected individuals taking ART with and without zidovudine at Addis Ababa, Ethiopia. Ethiop J Health Sci 28(1):73–8210.4314/ejhs.v28i1.9 ↗
65. Thrall JH, Ziessman HA (2003) Medicina nuclear, 2nd edn. Guanabara Koogan, Rio de Janeiro
66. Troutman MD, Thakker DR (2003) Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across Caco-2 cell monolayers. Pharm Res 20(8):1200–120910.1023/A:1025049014674 ↗
67. Tamir Z, Alemu J, Tsegaye A (2018b) Anemia among HIV infected individuals taking ART with and without zidovudine at Addis Ababa, Ethiopia. Ethiop J Health Sci 28(1):73–8210.4314/ejhs.v28i1.9 ↗
68. Tyagi P, Subramony JA (2018) Nanotherapeutics in oral and parenteral drug delivery: Key learnings and future outlooks as we think small. J Control Release 272:159–16810.1016/j.jconrel.2018.01.009 ↗
69. Venturini CG, Jäger E, Oliveira CP, Bernardi A, Battastini AMO, Guterres SS, Pohlmann AR (2011) Formulation of lipid core nanocapsules. Colloids Surf A Physicochem Eng Asp 375(1–3):200–20810.1016/j.colsurfa.2010.12.011 ↗
70. Wang F, Miao MX, Sun BB, Wang ZJ, Tang XG, Chen Y, Zhao KJ, Liu XD, Liu L (2017) Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp. Acta Pharmacol Sin 38(11):1554–156510.1038/aps.2017.54 ↗
71. Wang H, Wolock TM, Carter A, Nguyen G, Kyu HH, Gakidou E et al (2016) Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV 3(8):e361–e38710.1016/S2352-3018(16)30087-X ↗
72. WHO (2017) Fact sheet on HIV/AIDS. World Health Organization HIV/AIDS Department. http://www.who.int/mediacentre/factsheets/fs360/en/ . Accessed 2 Febr 2018
73. Woodruff MA, Hutmacher DW (2010) The return of a forgotten polymer—polycaprolactone in the 21st century. Prog Polym Sci 35(10):1217–125610.1016/j.progpolymsci.2010.04.002 ↗
74. Yameen B, Choi WI, Vilos C, Swami A, Shi J, Farokhzad OC (2014) Insight into nanoparticle cellular uptake and intracellular targeting. J Control Release 190:485–49910.1016/j.jconrel.2014.06.038 ↗