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Polymeric Nanoparticle Versus Liposome Formulations: Comparative Physicochemical and Metabolomic Studies as l-Carnitine Delivery Systems

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Abstract

l-Carnitine has attracted much more attention especially in the treatment of crucial diseases such as diabetes, regional slimming, and obesity because of its metabolic activities. However, because of its short half-life, low bioavailability, and inability to be stored in the body, frequent dosing is required. In this study, l-carnitine-loaded liposome (lipo-carnitine) and PLGA nanoparticle (nano-carnitine) formulations were prepared and characterized. For lipo-carnitine and nano-carnitine formulations, particle size values were 97.88 ± 2.96 nm and 250.90 ± 6.15 nm; polydispersity index values were 0.35 ± 0.01 and 0.22 ± 0.03; zeta potential values were 6.36 ± 0.54 mV and − 32.80 ± 2.26 mV; and encapsulation efficiency percentage values were 14.26 ± 3.52% and 21.93 ± 4.17%, respectively. Comparative in vitro release studies of novel formulations and solution of l-carnitine revealed that l-carnitine released 90% of its content at the end of 1st hour. On the other hand, lipo-carnitine and nano-carnitine formulations maintained a controlled-release profile for 12 h. The in vitro efficacy of the formulations on cardiac fibroblasts (CFs) was evaluated by metabolomic studies and pathway analysis. Besides the prolonged release, lipo-carnitine/nano-carnitine formulations were also found to be effective on amino acid, carbohydrate, and lipid metabolisms. As a result, innovative nano-formulations were successfully developed as an alternative to conventional preparations which are available on the market.

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References

  1. Bremer J. Carnitine-metabolism and functions. Physiol Rev. 1983;63(4):1420–80. https://doi.org/10.1152/physrev.1983.63.4.1420.

    Article  CAS  PubMed  Google Scholar 

  2. Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr. 1998;18:39–61. https://doi.org/10.1146/annurev.nutr.18.1.39.

    Article  CAS  PubMed  Google Scholar 

  3. Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K, Olyaeemanesh A. The effect of (L-) carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2016;17(10):970–6. https://doi.org/10.1111/obr.12436.

    Article  CAS  PubMed  Google Scholar 

  4. Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr. 2000;72(2):618S–23S. https://doi.org/10.1093/ajcn/72.2.618S.

    Article  CAS  PubMed  Google Scholar 

  5. Brass EP, Hiatt WR. The role of carnitine and carnitine supplementation during exercise in man and in individuals with special needs. J Am Coll Nutr. 1998;17(3):207–15. https://doi.org/10.1080/07315724.1998.10718750.

    Article  CAS  PubMed  Google Scholar 

  6. Ames BN, Liu J. Delaying the mitochondrial decay of aging with acetylcarnitine. Ann N Y Acad Sci. 2004;1033:108–16. https://doi.org/10.1196/annals.1297.073.

    Article  CAS  PubMed  Google Scholar 

  7. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol. 2003;18(2):61–71. https://doi.org/10.1097/00004850-200303000-00001.

    Article  PubMed  Google Scholar 

  8. Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34(5):1618–24. https://doi.org/10.1016/S0735-1097(99)00373-3.

    Article  CAS  PubMed  Google Scholar 

  9. Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud S, Shaiova L, et al. L-Carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Ann N Y Acad Sci. 2004;1033:168–76. https://doi.org/10.1196/annals.1320.016.

    Article  CAS  PubMed  Google Scholar 

  10. Graziano F, Bisonni R, Catalano V, Silva R, Rovidati S, Mencarini E, et al. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer. 2002;86(12):1854–7. https://doi.org/10.1038/sj.bjc.6600413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mingrone G, Greco AV, Capristo E, Benedetti G, Giancaterini A, De Gaetano A, et al. L-carnitine improves glucose disposal in type 2 diabetic patients. J Am Coll Nutr. 1999;18(1):77–82. https://doi.org/10.1080/07315724.1999.10718830.

    Article  CAS  PubMed  Google Scholar 

  12. Vidal-Casariego A, Burgos-Pelaez R, Martinez-Faedo C, Calvo-Gracia F, Valero-Zanuy MA, Luengo-Perez LM, et al. Metabolic effects of L-carnitine on type 2 diabetes mellitus: systematic review and meta-analysis. Exp Clin Endocrinol Diabetes. 2013;121(4):234–8. https://doi.org/10.1182/blood.V91.10.3817.

  13. Moretti S, Alesse E, Di Marzio L, Zazzeroni F, Ruggeri B, Marcellini S, et al. Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood. 1998;91(10):3817–24.

    Article  CAS  Google Scholar 

  14. Scarpini E, Sacilotto G, Baron P, Cusini M, Scarlato G. Effect of acetyl-L-carnitine in the treatment of painful peripheral neuropathies in HIV+ patients. J Peripher Nerv Syst. 1997;2(3):250–2.

    CAS  PubMed  Google Scholar 

  15. Matalliotakis I, Koumantaki Y, Evageliou A, Matalliotakis G, Goumenou A, Koumantakis E. L-carnitine levels in the seminal plasma of fertile and infertile men: correlation with sperm quality. Int J Fertil Womens Med. 2000;45(3):236–40.

    CAS  PubMed  Google Scholar 

  16. Costa M, Canale D, Filicori M, D’Lddio S, Lenzi A. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia. 1994;26(3):155–9. https://doi.org/10.1111/j.1439-0272.1994.tb00780.x.

    Article  CAS  PubMed  Google Scholar 

  17. Harper P, Elwin CE, Cederblad G. Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. Eur J Clin Pharmacol. 1988;35(5):555–62. https://doi.org/10.1007/BF00558253.

    Article  CAS  PubMed  Google Scholar 

  18. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet. 2003;42(11):941–67. https://doi.org/10.2165/00003088-200342110-00002.

    Article  CAS  PubMed  Google Scholar 

  19. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85. https://doi.org/10.1038/nm.3145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cao Y, Qu HJ, Li P, Wang CB, Wang LX, Han ZW. Single dose administration of L-carnitine improves antioxidant activities in healthy subjects. Tohoku J Exp Med. 2011;224(3):209–13. https://doi.org/10.1620/tjem.224.209.

    Article  CAS  PubMed  Google Scholar 

  21. Eroglu I, Ibrahim M. Liposome-ligand conjugates: a review on the current state of art. J Drug Target. 2020;28(3):225–44. https://doi.org/10.1080/1061186X.2019.1648479.

    Article  CAS  PubMed  Google Scholar 

  22. He H, Lu Y, Qi J, Zhu Q, Chen Z, Wu W. Adapting liposomes for oral drug delivery. Acta Pharm Sin B. 2019;9(1):36–48. https://doi.org/10.1016/j.apsb.2018.06.005.

    Article  PubMed  Google Scholar 

  23. Ling SSN, Yuen KH, Magosso E, Barker SA. Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats. J Pharm Pharmacol. 2009;61(4):445–9. https://doi.org/10.1211/jpp.61.04.0005.

    Article  CAS  PubMed  Google Scholar 

  24. Pantze SF, Parmentier J, Hofhaus G, Fricker G. Matrix liposomes: a solid liposomal formulation for oral administration. Eur J Lipid Sci Technol. 2014;116(9):1145–54. https://doi.org/10.1002/ejlt.201300409.

    Article  CAS  Google Scholar 

  25. Bardania H, Shojaosadati SA, Kobarfard F, Dorkoosh F, Zadeh ME, Naraki M, et al. Encapsulation of eptifibatide in RGD-modified nanoliposomes improves platelet aggregation inhibitory activity. J Thromb Thrombolysis. 2017;43(2):184–93. https://doi.org/10.1007/s11239-016-1440-6.

    Article  CAS  PubMed  Google Scholar 

  26. Singh RP, Gangadharappa HV, Mruthunjaya K. Phospholipids: unique carriers for drug delivery systems. J Drug Deliv Sci Technol. 2017;39:166–79. https://doi.org/10.1016/j.jddst.2017.03.027.

    Article  CAS  Google Scholar 

  27. Frezard F. Liposomes: from biophysics to the design of peptide vaccines. Braz J Med Biol Res. 1999;32(2):181–9. https://doi.org/10.1590/S0100-879X1999000200006.

    Article  CAS  PubMed  Google Scholar 

  28. Li J, Wang XL, Zhang T, Wang CL, Huang ZJ, Luo X, et al. A review on phospholipids and their main applications in drug delivery systems. Asian J Pharm Sci. 2015;10(2):81–98. https://doi.org/10.1016/j.ajps.2014.09.004.

    Article  Google Scholar 

  29. Eroglu I, Aslan M, Yaman U, Gultekinoglu M, Calamak S, Kart D, et al. Liposome-based combination therapy for acne treatment. J Liposome Res. 2019;30:1–11. https://doi.org/10.1080/08982104.2019.1630646.

    Article  CAS  Google Scholar 

  30. Sheikhsaran F, Sadeghpour H, Khalvati B, Entezar-Almahdi E, Dehshahri A. Tetraiodothyroacetic acid-conjugated polyethylenimine for integrin receptor mediated delivery of the plasmid encoding IL-12 gene. Colloids Surf B: Biointerfaces. 2017;150:426–36. https://doi.org/10.1016/j.colsurfb.2016.11.008.

    Article  CAS  PubMed  Google Scholar 

  31. Khalid M, El-Sawy HS. Polymeric nanoparticles: promising platform for drug delivery. Int J Pharm. 2017;528(1–2):675–91. https://doi.org/10.1016/j.ijpharm.2017.06.052.

    Article  CAS  Google Scholar 

  32. Masood F. Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Mater Sci Eng C. 2016;60:569–78. https://doi.org/10.1016/j.msec.2015.11.067.

    Article  CAS  Google Scholar 

  33. Sadeghpour H, Khalvati B, Entezar-Almahdi E, Savadi N, Alhashemi SH, Raoufi M, et al. Double domain polyethylenimine-based nanoparticles for integrin receptor mediated delivery of plasmid DNA. Sci Rep. 2018;8(1):1–12. https://doi.org/10.1038/s41598-018-25277-z.

    Article  CAS  Google Scholar 

  34. Bolhassani A, Javanzad S, Saleh T, Hashemi M, Aghasadeghi MR, Sadat SM. Polymeric nanoparticles potent vectors for vaccine delivery targeting cancer and infectious diseases. Hum Vacc Immunother. 2014;10(2):321–32. https://doi.org/10.4161/hv.26796.

    Article  CAS  Google Scholar 

  35. Ozcan I, Bouchemal K, Segura-Sanchez F, Ozer O, Guneri T, Ponchel G. Synthesis and characterization of surface-modified PBLG nanoparticles for bone targeting: in vitro and in vivo evaluations. J Pharm Sci. 2011;100(11):4877–87. https://doi.org/10.1002/jps.22678.

    Article  CAS  PubMed  Google Scholar 

  36. Toya Y, Shimizu H. Flux analysis and metabolomics for systematic metabolic engineering of microorganisms. Biotechnol Adv. 2013;31(6):818–26. https://doi.org/10.1016/j.biotechadv.2013.05.002.

    Article  CAS  PubMed  Google Scholar 

  37. Keibler MA, Fendt SM, Stephanopoulos G. Expanding the concepts and tools of metabolic engineering to elucidate cancer metabolism. Biotechnol Prog. 2012;28(6):1409–18. https://doi.org/10.1002/btpr.1629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Buescher JM, Antoniewicz MR, Boros LG, Burgess SC, Brunengraber H, Clish CB, et al. A roadmap for interpreting (13) C metabolite labeling patterns from cells. Curr Opin Biotechnol. 2015;34:189–201. https://doi.org/10.1016/j.copbio.2015.02.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Patti GJ, Yanes O, Siuzdak G. Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol. 2012;13(4):263–9. https://doi.org/10.1038/nrm3314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Moyon T, Le Marecel F, Qannari M, Vigneau E, Le Plain A, Courant F, et al. Statistical strategies for relating metabolomics and proteomics data: a real case study in nutrition research area. Metabolomics. 2012;8(6):1090–101. https://doi.org/10.1007/s11306-012-0415-7.

    Article  CAS  Google Scholar 

  41. Jansen JJ, Szymanska E, Hoefsloot HC, Smilde AK. Individual differences in metabolomics: individualised responses and between-metabolite relationships. Metabolomics. 2012;8(Suppl 1):94–104. https://doi.org/10.1007/s11306-012-0414-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. European Medicines Agency. ICH topic Q2 (R1), validation of analytical procedures: text and methodology. 1995. https://www.ich.org/page/quality-guidelines. Accessed 1 June 1995.

  43. Desai KGH, Park HJ. Recent developments in microencapsulation of food ingredients. Dry Technol. 2005;23(7):1361–94. https://doi.org/10.1081/DRT-200063478.

    Article  CAS  Google Scholar 

  44. Tanrıverdi ST, Özer Ö. Novel topical formulations of terbinafine-HCl for treatment of onychomycosis. Eur J Pharm Sci. 2013;48(4–5):628–36. https://doi.org/10.1016/j.ejps.2012.12.014.

    Article  CAS  PubMed  Google Scholar 

  45. Kumar GP, Rajeshwarrao P. Nonionic surfactant vesicular systems for effective drug delivery-an overview. Acta Pharm Sin B. 2011;1(4):208–19. https://doi.org/10.1016/j.apsb.2011.09.002.

    Article  CAS  Google Scholar 

  46. Choi M, Maibach H. Liposomes and niosomes as topical drug delivery systems. Skin Pharmacol Physiol. 2005;18(5):209–19. https://doi.org/10.1159/000086666.

    Article  CAS  PubMed  Google Scholar 

  47. 5th European Pharmacopoeia. European Directorate for the Quality of Medicines. Strasbourg2007.

  48. International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use. Validation of analytical procedures: text and methodology ICH-Q2B. Geneva1996. https://www.fda.gov/media/71725/download. Accessed Nov 1996.

  49. Mura S, Hillaireau H, Nicolas J, Le Droumaguet B, Gueutin C, Zanna S, et al. Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells. Int J Nanomedicine. 2011;6:2591–605. https://doi.org/10.2147/IJN.S24552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sengel Turk CT, Bayindir ZS, Badilli U. Preparation of polymeric nanoparticles using different stabilizing agents. J Fac Pharm Ankara. 2009;38(4):257–68.

    CAS  Google Scholar 

  51. Grit M, Crommelin DJ. Chemical stability of liposomes: implications for their physical stability. Chem Phys Lipids. 1993;64(1–3):3–18. https://doi.org/10.1016/0009-3084(93)90053-6.

    Article  CAS  PubMed  Google Scholar 

  52. Yael E. Formulation and biopharmaceutical evaluation of lipid nanocarriers with incorporated lidocaine hydrochloride: Lithuanian University of Health Sciences; 2017.

  53. Song CK, Balakrishnan P, Shim CK, Chung SJ, Chong S, Kim DD. A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: characterization and in vitro/in vivo evaluation. Colloids Surf B: Biointerfaces. 2012;92:299–304. https://doi.org/10.1016/j.colsurfb.2011.12.004.

    Article  CAS  PubMed  Google Scholar 

  54. Refai H, Hassan D, Abdelmonem R. Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate. Drug Deliv. 2017;24(1):278–88. https://doi.org/10.1080/10717544.2016.1247925.

    Article  CAS  PubMed  Google Scholar 

  55. Wieber A, Selzer T, Kreuter J. Characterisation and stability studies of a hydrophilic decapeptide in different adjuvant drug delivery systems: a comparative study of PLGA nanoparticles versus chitosan-dextran sulphate microparticles versus DOTAP-liposomes. Int J Pharm. 2011;421(1):151–9. https://doi.org/10.1016/j.ijpharm.2011.09.011.

    Article  CAS  PubMed  Google Scholar 

  56. Darvishi B, Manoochehri S, Kamalinia G, Samadi N, Amini M, Mostafavi SH, et al. Preparation and antibacterial activity evaluation of 18-beta-glycyrrhetinic acid loaded PLGA nanoparticles. Iran J Pharm Res. 2015;14(2):373–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Dias DJS, Joanitti GA, Azevedo RB, Silva LP, Lunardi CN, Gomes AJ. Chlorambucil encapsulation into PLGA nanoparticles and cytotoxic effects in breast cancer cell. J Biophys Chem. 2015;6(1):1–13. https://doi.org/10.4236/jbpc.2015.61001.

    Article  CAS  Google Scholar 

  58. Lamster IB, Mandella RD, Zove SM, Harper DS. The polyamines putrescine, spermidine and spermine in human gingival crevicular fluid. Arch Oral Biol. 1987;32(5):329–33. https://doi.org/10.1016/0003-9969(87)90087-2.

    Article  CAS  PubMed  Google Scholar 

  59. Duangjit S, Pamornpathomkul B, Opanasopit P, Rojanarata T, Obata Y, Takayama K, et al. Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes. Int J Nanomedicine. 2014;9:2005–17. https://doi.org/10.2147/IJN.S60674.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Chu BS, Ichikawa S, Kanafusa S, Nakajima M. Preparation and characterization of beta-carotene nanodispersions prepared by solvent displacement technique. J Agric Food Chem. 2007;55(16):6754–60. https://doi.org/10.1021/jf063609d.

    Article  CAS  PubMed  Google Scholar 

  61. Baysal I, Ucar G, Gultekinoglu M, Ulubayram K, Yabanoglu-Ciftci S. Donepezil loaded PLGA-b-PEG nanoparticles: their ability to induce destabilization of amyloid fibrils and to cross blood brain barrier in vitro. J Neural Transm (Vienna). 2017;124(1):33–45. https://doi.org/10.1007/s00702-016-1527-4.

    Article  CAS  Google Scholar 

  62. Tuncay M, Calis S, Kas HS, Ercan MT, Peksoy I, Hincal AA. Diclofenac sodium incorporated PLGA (50:50) microspheres: formulation considerations and in vitro/in vivo evaluation. Int J Pharm. 2000;195(1–2):179–88. https://doi.org/10.1016/S0378-5173(99)00394-4.

    Article  CAS  PubMed  Google Scholar 

  63. Nounou MM, El-Khordagui LK, Khalafallah NA, Khalil SA. In vitro release of hydrophilic and hydrophobic drugs from liposomal dispersions and gels. Acta Pharma. 2006;56(3):311–24.

    CAS  Google Scholar 

  64. Miao ZL, Deng YJ, Du HY, Suo XB, Wang XY, Wang X, et al. Preparation of a liposomal delivery system and its in vitro release of rapamycin. Exp Ther Med. 2015;9(3):941–6.

    Article  CAS  Google Scholar 

  65. Joseph J, Vedha BNV, Ramya DD. Experimental optimization of lornoxicam liposomes for sustained topical delivery. Eur J Pharm Sci. 2018;112:38–51. https://doi.org/10.1016/j.ejps.2017.10.032.

    Article  CAS  PubMed  Google Scholar 

  66. Chibas LC, Cintra PP, Moreira MR, Goulart MO, Ambrosio SR, Veneziani RCS, et al. Polyalthic acid in polymeric nanoparticles causes selective growth inhibition and genotoxicity in MCF-7 cells. Nat Prod Commun. 2019;14(4). https://doi.org/10.1177/1934578X19842702.

  67. Hines DJ, Kaplan DL. Poly (lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights. Crit Rev Ther Drug. 2013;30(3):257–76.

    Article  CAS  Google Scholar 

  68. Eroğlu H, Haidar MK, Nemutlu E, Öztürk Ş, Bayram C, Ulubayram K, et al. Dual release behavior of atorvastatin and alpha-lipoic acid from PLGA microspheres for the combination therapy in peripheral nerve injury. J Drug Deliv Sci Technol. 2017;39:455–66. https://doi.org/10.1016/j.jddst.2017.04.028.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank HUNIKAL – HUNITEK Central Laboratories for their valuable support in the experimental part.

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Authors and Affiliations

  1. Nanotechnology and Nanomedicine Division, Institute for Graduate Studies in Science and Engineering, Hacettepe University, Ankara, Turkey

    Merve Yaşacan, Kezban Ulubayram & İpek Eroğlu

  2. ASELSAN Inc., Teknopark Istanbul, 34906, Istanbul, Turkey

    Merve Yaşacan

  3. Department of Biochemistry, Faculty of Pharmacy, Lokman Hekim University, Ankara, Turkey

    Açelya Erikçi

  4. Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Cemil Can Eylem & Emirhan Nemutlu

  5. Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Samiye Yabanoğlu Çiftçi

  6. Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Kezban Ulubayram & İpek Eroğlu

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  1. Merve Yaşacan
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Yaşacan, M., Erikçi, A., Eylem, C.C. et al. Polymeric Nanoparticle Versus Liposome Formulations: Comparative Physicochemical and Metabolomic Studies as l-Carnitine Delivery Systems. AAPS PharmSciTech 21, 308 (2020). https://doi.org/10.1208/s12249-020-01852-4

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