NANO-ENABLED THERAPEUTICS: EXPLORING BIOEQUIVALENCE AND BIOAVAILABILITY FRONTIERS
DOI:
https://doi.org/10.22159/ijap.2025v17i6.55458Keywords:
Nanoformulations, Bioequivalence, Bioavailability, Pharmacokinetics, RegulationsAbstract
The advancement of nanotechnology has significantly transformed pharmaceutical sciences, especially in enhancing the bioavailability and bioequivalence (BE) of drugs with poor solubility and permeability. Nanoparticulate drug delivery systems including nanoparticles, nanocrystals, nanoemulsions, and liposomes exhibit unique physicochemical properties such as increased surface area, improved dissolution rates, and enhanced permeability. These characteristics collectively contribute to superior therapeutic efficacy. For example, a 25-fold increase in the bioavailability of poorly soluble drugs such as retinoic acid has been reported by the use of solid lipid nanoparticles (SLNs), which act as protective lipid matrices, augmenting drug stability and allowing sustained release. This comprehensive review explores the fundamental concepts of bioavailability and BE as they pertain to nanoformulations, focusing on key factors that influence the absorption, distribution, metabolism, and excretion of nanosized drugs. It emphasizes the mechanistic pathways by which nanocarriers overcome biological barriers, including the gastrointestinal (GI) tract and first-pass metabolism, thereby improving pharmacokinetic (PK) profiles. Furthermore, the review discusses analytical methodologies and regulatory considerations critical to evaluating the BE of nanoformulated drugs. It highlights challenges in establishing equivalency arising from altered pharmacokinetic and pharmacodynamic (PD) behaviors unique to these formulations. A comparative analysis of conventional versus nanoformulated drugs illustrates the clinical implications of nanotechnology in drug delivery, such as dose reduction, improved patient compliance, and minimized adverse effects. Additionally, recent advancements in formulation strategies and characterization techniques are synthesized, showcasing how surface modifications, size optimization, and targeting moieties enhance oral bioavailability. By evaluating preclinical and clinical studies, this article provides valuable insights into the translational potential of nanoformulations. It also identifies existing gaps and future directions in regulatory frameworks and standardized BE testing. In summary, this review offers a holistic understanding of nanotechnology’s role in improving drug bioavailability and BE, serving as an essential resource for pharmaceutical scientists, clinicians, and regulatory authorities aiming to leverage nanoformulations for enhanced therapeutic outcomes. Despite notable progress, significant challenges remain especially in achieving scalable manufacturing, ensuring reproducibility of formulations and navigating complex regulatory landscapes. These challenges stress on the urgent need for internationally harmonized standards and robust quality control systems to support clinical translation.
References
1. Chaturvedi S, Mishra R. Insight into delivery approaches for biopharmaceutics classification system class ii and iv drugs. Drug Deliv Lett. 2020;10(4):255-77. doi: 10.2174/2210303110999200712185109.
2. Kumari L, Choudhari Y, Patel P, Gupta GD, Singh D, Rosenholm JM. Advancement in solubilization approaches: a step towards bioavailability enhancement of poorly soluble drugs. Life (Basel). 2023;13(5):1099. doi: 10.3390/life13051099, PMID 37240744.
3. Hu L, Tang X, Cui F. Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol. 2004 Dec;56(12):1527-35. doi: 10.1211/0022357044959, PMID 15563759.
4. Fabiano A, Piras AM, Uccello Barretta G, Balzano F, Cesari A, Testai L. Impact of mucoadhesive polymeric nanoparticulate systems on oral bioavailability of a macromolecular model drug. Eur J Pharm Biopharm. 2018 Sep 1;130:281-9. doi: 10.1016/j.ejpb.2018.07.010, PMID 30006244.
5. Reboredo C, Gonzalez Navarro CJ, Martinez Lopez AL, Martinez Oharriz C, Sarmento B, Irache JM. Zein based nanoparticles as oral carriers for insulin delivery. Pharmaceutics. 2021;14(1):39. doi: 10.3390/pharmaceutics14010039, PMID 35056935.
6. Cheng X, Han X, Si J, Dong C, Ji Z, Zhao S. Cationic curcumin nanocrystals liposomes for improved oral bioavailability: formulation development optimization in vitro and in vivo evaluation. Pharmaceutics. 2024;16(9):1155. doi: 10.3390/pharmaceutics16091155, PMID 39339192.
7. Quadir SS, Joshi G, Saharan V, Mangesh H, Choudhary D, Yadav K. A review on nanostructured lipid carriers as promising drug delivery vehicle to target various cancers via oral route: a step towards chemotherapy at home CNANOM. 2024;14(2):127-42. doi: 10.2174/0124681873272867231113192452.
8. Dasgupta A, Sofias AM, Kiessling F, Lammers T. Nanoparticle delivery to tumours: from EPR and ATR mechanisms to clinical impact. Nat Rev Bioeng. 2024;2(9):714-6. doi: 10.1038/s44222-024-00203-3, PMID 39376248.
9. Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv Drug Deliv Rev. 2012;64(6):557-70. doi: 10.1016/j.addr.2011.12.009, PMID 22212900.
10. Dahan A, Miller JM, Amidon GL. Prediction of solubility and permeability class membership: provisional BCS classification of the world’s top oral drugs. AAPS J. 2009;11(4):740-6. doi: 10.1208/s12248-009-9144-x, PMID 19876745.
11. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11-23. doi: 10.1007/s11095-004-9004-4, PMID 15771225.
12. U.S. Food and Drug Administration. Guidance for Industry: Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs-General Considerations. Draft Guidance; 2014. Available from: https://www.fda.gov/media/88254/download.
13. Stokvis E, Rosing H, Beijnen JH. Liquid chromatography mass spectrometry for the quantitative bioanalysis of anticancer drugs. Mass Spectrom Rev. 2005;24(6):887-917. doi: 10.1002/mas.20046, PMID 15599948.
14. U.S. Food and Drug Administration. Guidance for industry: bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA. Draft guidance. Available from: https://www.fda.gov/media/87219/download. [Last accessed on 09 Jun 2025].
15. European Medicines Agency. Guideline on the investigation of bioequivalence. EMA/CHMP/EWP/QWP/1401/98 Rev; 2010 Jan. p. 1. Available from: from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf. [Last accessed on 09 Jun 2025].
16. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286. doi: 10.3389/fphar.2015.00286, PMID 26648870.
17. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761-9. doi: 10.1038/sj.clpt.6100400, PMID 17957183.
18. Jones HM, Chen Y, Gibson C, Heimbach T, Parrott N, Peters SA. Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective. Clin Pharmacol Ther. 2015;97(3):247-62. doi: 10.1002/cpt.37, PMID 25670209.
19. Ozbek O, Genc DE, O Ulgen K. Advances in physiologically based pharmacokinetic (PBPK) modeling of nanomaterials. ACS Pharmacol Transl Sci. 2024;7(8):2251-79. doi: 10.1021/acsptsci.4c00250, PMID 39144562.
20. Patra JK, Das G, Fraceto LF, Campos EV, Rodriguez Torres MD, Acosta Torres LS. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):71. doi: 10.1186/s12951-018-0392-8, PMID 30231877.
21. Augustine R, Hasan A, Primavera R, Wilson RJ, Thakor AS, Kevadiya BD. Cellular uptake and retention of nanoparticles: insights on particle properties and interaction with cellular components. Mater Today Commun. 2020;25:101692. doi: 10.1016/j.mtcomm.2020.101692.
22. Ma P, Mumper RJ. Paclitaxel nano-delivery systems: a comprehensive review. J Nanomed Nanotechnol. 2013;4(2):1000164. doi: 10.4172/2157-7439.1000164, PMID 24163786.
23. Abd Elghany AE, El Garhy O, Fatease AA, Alamri AH, Abdelkader H. Enhancing oral bioavailability of simvastatin using uncoated and polymer coated solid lipid nanoparticles. Pharmaceutics. 2024;16(6):763. doi: 10.3390/pharmaceutics16060763, PMID 38931885.
24. Kawano K, Furuya A, Matsuda Y, Kimura C, Yamaguchi K, Wakabayashi S. Preparation of liposomes co-encapsulating doxorubicin and mifepristone for treating multidrug resistant cancer. J Drug Deliv Sci Technol. 2023;85:104605. doi: 10.1016/j.jddst.2023.104605.
25. Anuar N, Sabri AH, Bustami Effendi TJ, Abdul Hamid K. Development and characterisation of ibuprofen loaded nanoemulsion with enhanced oral bioavailability. Heliyon. 2020;6(7):e04570. doi: 10.1016/j.heliyon.2020.e04570, PMID 32775730.
26. Ige PP, Baria RK, Gattani SG. Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability. Colloids Surf B Biointerfaces. 2013;108:366-73. doi: 10.1016/j.colsurfb.2013.02.043, PMID 23602990.
27. Ismailos G, Reppas C, Macheras P. Enhancement of cyclosporin a solubility by d-alphatocopheryl polyethylene glycol-1000 succinate (TPGS). Eur J Pharm Sci. 1994;1(5):269-71. doi: 10.1016/0928-0987(94)90021-3.
28. Li H, Chen X, Rao S, Zhou M, Lu J, Liang D. Recent development of micro-nano carriers for oral antineoplastic drug delivery. Mater Today Bio. 2025;30:101445. doi: 10.1016/j.mtbio.2025.101445, PMID 39866789.
29. Lou J, Duan H, Qin Q, Teng Z, Gan F, Zhou X. Advances in oral drug delivery systems: challenges and opportunities. Pharmaceutics. 2023;15(2):484. doi: 10.3390/pharmaceutics15020484, PMID 36839807.
30. Liu Y, Liang Y, Yuhong J, Xin P, Han JL, Du Y. Advances in nanotechnology for enhancing the solubility and bioavailability of poorly soluble drugs. Drug Des Dev Ther. 2024;18:1469-95. doi: 10.2147/DDDT.S447496, PMID 38707615.
31. Sun R, Chen Y, Pei Y, Wang W, Zhu Z, Zheng Z. The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers. Heliyon. 2024;10(18):e38165. doi: 10.1016/j.heliyon.2024.e38165, PMID 39364250.
32. Lin CH, Chen CH, Lin ZC, Fang JY. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. J Food Drug Anal. 2017;25(2):219-34. doi: 10.1016/j.jfda.2017.02.001, PMID 28911663.
33. 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. doi: 10.1016/j.apsb.2018.06.005, PMID 30766776.
34. Preeti S, Sambhakar S, Malik R, Bhatia S, Al Harrasi A, Rani C. Nanoemulsion: an emerging novel technology for improving the bioavailability of drugs. Scientifica. 2023;2023:6640103. doi: 10.1155/2023/6640103, PMID 37928749.
35. Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water soluble drugs. Asian J Pharm Sci. 2015;10(1):13-23. doi: 10.1016/j.ajps.2014.08.005.
36. Nguyen TT, Duong VA, Maeng HJ. Pharmaceutical formulations with P-glycoprotein inhibitory effect as promising approaches for enhancing oral drug absorption and bioavailability. Pharmaceutics. 2021;13(7):1103. doi: 10.3390/pharmaceutics13071103, PMID 34371794.
37. Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135-46. doi: 10.1016/j.jconrel.2010.08.027, PMID 20797419.
38. Beloqui A, Solinis MA, Rodriguez Gascon A, Almeida AJ, Preat V. Nanostructured lipid carriers: promising drug delivery systems for future clinics. Nanomedicine. 2016;12(1):143-61. doi: 10.1016/j.nano.2015.09.004, PMID 26410277.
39. Kurul F, Turkmen H, Cetin AE, Topkaya SN. Nanomedicine: how nanomaterials are transforming drug delivery bio-imaging, and diagnosis. Next Nanotechnol. 2025;7:100129. doi: 10.1016/j.nxnano.2024.100129.
40. Liu Y, Liang Y, Yuhong J, Xin P, Han JL, Du Y. Advances in nanotechnology for enhancing the solubility and bioavailability of poorly soluble drugs. Drug Des Dev Ther. 2024;18:1469-95. doi: 10.2147/DDDT.S447496, PMID 38707615.
41. Pınar SG, Oktay AN, Karakucuk AE, Celebi N. Formulation strategies of nanosuspensions for various administration routes. Pharmaceutics. 2023;15(5):1520. doi: 10.3390/pharmaceutics15051520, PMID 37242763.
42. Pujitha R, Chellakumari SD, Damayanthi RD, Aakash NS, Aswin Kumar AM. Engineered nanocrystals for poorly soluble drug delivery: a review. Indian J Pharm Sci. 2024;86(3):742-54. doi: 10.36468/pharmaceutical-sciences.1332.
43. Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol. 2004;56(7):827-40. doi: 10.1211/0022357023691, PMID 15233860.
44. M Ways TM, Lau WM, Khutoryanskiy VV. Chitosan and its derivatives for application in mucoadhesive drug delivery systems. Polymers. 2018;10(3):267. doi: 10.3390/polym10030267, PMID 30966302.
45. Cui F, Qian F, Yin C. Preparation and characterization of mucoadhesive polymer coated nanoparticles. Int J Pharm. 2006;316(1-2):154-61. doi: 10.1016/j.ijpharm.2006.02.031, PMID 16567070.
46. Takeuchi H, Matsui Y, Yamamoto H, Kawashima Y. Mucoadhesive properties of carbopol or chitosan coated liposomes and their effectiveness in the oral administration of calcitonin to rats. J Control Release. 2003;86(2-3):235-42. doi: 10.1016/S0168-3659(02)00411-X, PMID 12526820.
47. Gao H, Yang Z, Zhang S, Cao S, Shen S, Pang Z. Ligand modified nanoparticles increases cell uptake alters endocytosis and elevates glioma distribution and internalization. Sci Rep. 2013;3:2534. doi: 10.1038/srep02534, PMID 23982586.
48. Batrakova EV, Kabanov AV. Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release. 2008;130(2):98-106. doi: 10.1016/j.jconrel.2008.04.013, PMID 18534704.
49. Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Control Release. 2010;145(3):182-95. doi: 10.1016/j.jconrel.2010.01.036, PMID 20226220.
50. Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231-48. doi: 10.1038/nrd2197, PMID 17330072.
51. Pouton CW. Formulation of poorly water soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29(3-4):278-87. doi: 10.1016/j.ejps.2006.04.016, PMID 16815001.
52. Haddadzadegan S, Dorkoosh F, Bernkop Schnürch A. Oral delivery of therapeutic peptides and proteins: technology landscape of lipid based nanocarriers. Adv Drug Deliv Rev. 2022;182:114097. doi: 10.1016/j.addr.2021.114097, PMID 34999121.
53. Chavanpatil MD, Khdair A, Gerard B, Bachmeier C, Miller DW, Shekhar MP. Surfactant polymer nanoparticles overcome P-glycoprotein mediated drug efflux. Mol Pharm. 2007;4(5):730-8. doi: 10.1021/mp070024d, PMID 17705442.
54. Pridgen EM, Alexis F, Farokhzad OC. Polymeric nanoparticle drug delivery technologies for oral delivery applications. Expert Opin Drug Deliv. 2015;12(9):1459-73. doi: 10.1517/17425247.2015.1018175, PMID 25813361.
55. Torchilin VP. Multifunctional stimuli sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov. 2014;13(11):813-27. doi: 10.1038/nrd4333, PMID 25287120.
56. Mura S, Nicolas J, Couvreur P. Stimuli responsive nanocarriers for drug delivery. Nat Mater. 2013;12(11):991-1003. doi: 10.1038/nmat3776, PMID 24150417.
57. Kesisoglou F, Panmai S, Wu Y. Nanosizing oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59(7):631-44. doi: 10.1016/j.addr.2007.05.003, PMID 17601629.
58. Bonhoeffer B, Kordikowski A, John E, Juhnke M. Numerical modeling of the dissolution of drug nanocrystals and its application to industrial product development. ADMET DMPK. 2022;10(4):253-87. doi: 10.5599/admet.1437, PMID 36578561.
59. Horter D, Dressman JB. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev. 2001;46(1-3):75-87. doi: 10.1016/s0169-409x(00)00130-7, PMID 11259834.
60. Subramanian DA, Langer R, Traverso G. Mucus interaction to improve gastrointestinal retention and pharmacokinetics of orally administered nano-drug delivery systems. J Nanobiotechnology. 2022;20(1):362. doi: 10.1186/s12951-022-01539-x, PMID 35933341.
61. Wu JR, Hernandez Y, Miyasaki KF, Kwon EJ. Engineered nanomaterials that exploit blood brain barrier dysfunction for delivery to the brain. Adv Drug Deliv Rev. 2023;197:114820. doi: 10.1016/j.addr.2023.114820, PMID 37054953.
62. Hansen ME, Ibrahim Y, Desai TA, Koval M. Nanostructure mediated transport of therapeutics through epithelial barriers. Int J Mol Sci. 2024;25(13):7098. doi: 10.3390/ijms25137098, PMID 39000205.
63. Rama A, Govindan I, Kailas AA, Annadurai T, Lewis SA, Ranganath Pai S. Drug delivery to the lymphatic system: the road less travelled. J Appl Pharm Sci. 2024;14(6):1-10. doi: 10.7324/JAPS.2024.180277.
64. Yang D, Zeng H, Zhuang Y, Jiang S, Pan W. Nanodrug delivery materials for digestive system diseases. APL Mater. 2024;12(6):060603. doi: 10.1063/5.0214020.
65. Ochubiojo M, Chinwude I, Ibanga E, Ifianyi S. Nanotechnology in drug delivery. In: Sezer AD, editor. Recent advances in novel drug carrier systems. InTech; 2012. p. 143-66. doi: 10.5772/51384.
66. Tong L, Zhou Z, Wang G, Wu C. A self-microemulsion enhances oral absorption of docetaxel by inhibiting P-glycoprotein and CYP metabolism. Drug Deliv Transl Res. 2023;13(4):983-93. doi: 10.1007/s13346-022-01255-x, PMID 36515864.
67. Bao H, Zhang Q, Yan Z. The impact of camptothecin encapsulated poly(lactic-co-glycolic acid) nanoparticles on the activity of cytochrome P450 in vitro. Int J Nanomedicine. 2019;14:383-91. doi: 10.2147/IJN.S188984, PMID 30662262.
68. Lu B, LV X, Le Y. Chitosan modified PLGA nanoparticles for control released drug delivery. Polymers. 2019;11(2):304. doi: 10.3390/polym11020304, PMID 30960288.
69. Natarajan JV, Darwitan A, Barathi VA, Ang M, Htoon HM, Boey F. Sustained drug release in nanomedicine: a long acting nanocarrier based formulation for glaucoma. ACS Nano. 2014;8(1):419-29. doi: 10.1021/nn4046024, PMID 24392729.
70. Muhlebach S. Regulatory challenges of nanomedicines and their follow on versions: a generic or similar approach? Adv Drug Deliv Rev. 2018;131:122-31. doi: 10.1016/j.addr.2018.06.024, PMID 29966685.
71. Tinkle S, McNeil SE, Muhlebach S, Bawa R, Borchard G, Barenholz YC. Nanomedicines: addressing the scientific and regulatory gap. Ann N Y Acad Sci. 2014;1313(1):35-56. doi: 10.1111/nyas.12403, PMID 24673240.
72. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):57. doi: 10.3390/pharmaceutics10020057, PMID 29783687.
73. Nogueira SS, Samaridou E, Simon J, Frank S, Beck Broichsitter M, Mehta A. Analytical techniques for the characterization of nanoparticles for mRNA delivery. Eur J Pharm Biopharm. 2024;198:114235. doi: 10.1016/j.ejpb.2024.114235, PMID 38401742.
74. Xie Y, Shao N, Jin Y, Zhang L, Jiang H, Xiong N. Determination of non-liposomal and liposomal doxorubicin in plasma by LC–MS/MS coupled with an effective solid phase extraction: in comparison with ultrafiltration technique and application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1072:149-60. doi: 10.1016/j.jchromb.2017.11.020, PMID 29175695.
75. Mortier KA, Lambert WE. Determination of unbound docetaxel and paclitaxel in plasma by ultrafiltration and liquid chromatography tandem mass spectrometry. J Chromatogr A. 2006;1108(2):195-201. doi: 10.1016/j.chroma.2005.12.103, PMID 16472531.
76. Mead H, Paraskevopoulou V, Smith N, Gibson R, Amerio Cox M, Taylor Vine G. Developing a robust in vitro release method for a polymeric nanoparticle: challenges and learnings. Int J Pharm. 2023;644:123317. doi: 10.1016/j.ijpharm.2023.123317, PMID 37586575.
77. Fluhmann B, Ntai I, Borchard G, Simoens S, Muhlebach S. Nanomedicines: the magic bullets reaching their target? Eur J Pharm Sci. 2019;128:73-80. doi: 10.1016/j.ejps.2018.11.019, PMID 30465818.
78. De Vlieger JS, Crommelin DJ, Tyner K, Drummond DC, Jiang W, McNeil SE. Report of the AAPS guidance forum on the fda draft guidance for industry: drug products including biological products that contain nanomaterials. AAPS J. 2019;21(4):56. doi: 10.1208/s12248-019-0329-7, PMID 30997588.
79. Borchard G, Fluhmann B, Muhlebach S. Nanoparticle iron medicinal products requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies. Regul Toxicol Pharmacol. 2012;64(2):324-8. doi: 10.1016/j.yrtph.2012.08.009, PMID 22951348.
80. Li SD, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm. 2008;5(4):496-504. doi: 10.1021/mp800049w, PMID 18611037.
81. Musazzi UM, Marini V, Casiraghi A, Minghetti P. Is the European regulatory framework sufficient to assure the safety of citizens using health products containing nanomaterials? Drug Discov Today. 2017;22(6):870-82. doi: 10.1016/j.drudis.2017.01.016, PMID 28189800.
82. Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nat Nanotechnol. 2007;2(8):469-78. doi: 10.1038/nnano.2007.223, PMID 18654343.
83. Johnston HJ, Hutchison G, Christensen FM, Peters S, Hankin S, Stone V. A review of the in vivo and in vitro toxicity of silver and gold particulates: particle attributes and biological mechanisms responsible for the observed toxicity. Crit Rev Toxicol. 2010;40(4):328-46. doi: 10.3109/10408440903453074, PMID 20128631.
84. Mourdikoudis S, Pallares RM, Thanh NT. Characterization techniques for nanoparticles: comparison and complementarity upon studying nanoparticle properties. Nanoscale. 2018;10(27):12871-934. doi: 10.1039/c8nr02278j, PMID 29926865.
85. Bamal D, Singh A, Chaudhary G, Kumar M, Singh M, Rani N. Silver nanoparticles biosynthesis characterization antimicrobial activities applications cytotoxicity and safety issues: an updated review. Nanomaterials (Basel). 2021;11(8):2086. doi: 10.3390/nano11082086, PMID 34443916.
86. Tekkeli SE, Kiziltas MV. Current HPLC methods for assay of nano drug delivery systems. Curr Top Med Chem. 2017;17(13):1588-94. doi: 10.2174/1568026616666161222112305, PMID 28017146.
87. Song JG, Baral KC, Kim GL, Park JW, Seo SH, Kim DH. Quantitative analysis of therapeutic proteins in biological fluids: recent advancement in analytical techniques. Drug Deliv. 2023;30(1):2183816. doi: 10.1080/10717544.2023.2183816, PMID 36880122.
88. Huang Y, Yu Q, Chen Z, Wu W, Zhu Q, Lu Y. In vitro and in vivo correlation for lipid based formulations: current status and future perspectives. Acta Pharmacol Sin B. 2021;11(8):2469-87. doi: 10.1016/j.apsb.2021.03.025, PMID 34522595.
89. Otsuka K, Shono Y, Dressman J. Coupling biorelevant dissolution methods with physiologically based pharmacokinetic modelling to forecast in vivo performance of solid oral dosage forms. J Pharm Pharmacol. 2013;65(7):937-52. doi: 10.1111/jphp.12059, PMID 23738721.
90. Lin Z, Aryal S, Cheng YH, Gesquiere AJ. Integration of in vitro and in vivo models to predict cellular and tissue dosimetry of nanomaterials using physiologically based pharmacokinetic modeling. ACS Nano. 2022;16(12):19722-54. doi: 10.1021/acsnano.2c07312, PMID 36520546.
91. Hh B, MM, GB, AD, GH, WJ. The Global Bioequivalence Harmonisation Initiative (GBHI): report of EUFEPS/AAPS fourth conference. Eur J Pharm Sci. 2021;167:105987. doi: 10.1016/j.ejps.2021.105987, PMID 34481066.
92. Valcourt DM, Kapadia CH, Scully MA, Dang MN, Day ES. Best practices for preclinical in vivo testing of cancer nanomedicines. Adv Healthc Mater. 2020;9(12):e2000110. doi: 10.1002/adhm.202000110, PMID 32367687.
93. Fonseca Gomes J, Loureiro JA, Tanqueiro SR, Mouro FM, Ruivo P, Carvalho T. In vivo bio-distribution and toxicity evaluation of polymeric and lipid based nanoparticles: a potential approach for chronic diseases treatment. Int J Nanomedicine. 2020;15:8609-21. doi: 10.2147/IJN.S267007, PMID 33177821.
94. Beach MA, Nayanathara U, Gao Y, Zhang C, Xiong Y, Wang Y. Polymeric nanoparticles for drug delivery. Chem Rev. 2024;124(9):5505-616. doi: 10.1021/acs.chemrev.3c00705, PMID 38626459.
95. Khan KU, Minhas MU, Badshah SF, Suhail M, Ahmad A, Ijaz S. Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs. Life Sci. 2022;291:120301. doi: 10.1016/j.lfs.2022.120301, PMID 34999114.
96. Kalaydina RV, Bajwa K, Qorri B, De Carlo A, Szewczuk MR. Recent advances in ‘smart’ delivery systems for extended drug release in cancer therapy. Int J Nanomedicine. 2018;13:4727-45. doi: 10.2147/IJN.S168053, PMID 30154657.
97. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle based drug and gene delivery. Adv Drug Deliv Rev. 2016;99(A):28-51. doi: 10.1016/j.addr.2015.09.012, PMID 26456916.
98. Anselmo AC, Mitragotri S. Nanoparticles in the clinic: an update. Bioeng Transl Med. 2019;4(3):e10143. doi: 10.1002/btm2.10143, PMID 31572799.
99. Mehnert W, Mader K. Solid lipid nanoparticles. Adv Drug Deliv Rev. 2012;64:83-101. doi: 10.1016/j.addr.2012.09.021.
100. Kumari M, Acharya A, Krishnamurthy PT. Antibody conjugated nanoparticles for target specific drug delivery of chemotherapeutics. Beilstein J Nanotechnol. 2023;14:912-26. doi: 10.3762/bjnano.14.75, PMID 37701520.
101. Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR. Nanoparticle based medicines: a review of FDA-approved materials and clinical trials to date. Pharm Res. 2016;33(10):2373-87. doi: 10.1007/s11095-016-1958-5, PMID 27299311.
102. Ewii UE, Attama AA, Olorunsola EO, Onugwu AL, Nwakpa FU, Anyiam C. Nanoparticles for drug delivery: insight into in vitro and in vivo drug release from nanomedicines. Nano TransMed. 2025;4:100083. doi: 10.1016/j.ntm.2025.100083.
103. Maheshwari K, Gottemukkula L. A review of nanogels as novel drug delivery systems. Asian J Pharm Clin Res. 2023;16(4):10-7. doi: 10.22159/ajpcr.2023.v16i4.46790.
104. Abdifetah O, Na Bangchang K. Pharmacokinetic studies of nanoparticles as a delivery system for conventional drugs and herb derived compounds for cancer therapy: a systematic review. Int J Nanomedicine. 2019;14:5659-77. doi: 10.2147/IJN.S213229, PMID 31632004.
105. Petschauer JS, Madden AJ, Kirschbrown WP, Song G, Zamboni WC. The effects of nanoparticle drug loading on the pharmacokinetics of anticancer agents. Nanomedicine (Lond). 2015;10(3):447-63. doi: 10.2217/nnm.14.179, PMID 25707978.
106. Muhamad N, Plengsuriyakarn T, Na Bangchang K. Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: a systematic review. Int J Nanomedicine. 2018;13:3921-35. doi: 10.2147/IJN.S165210, PMID 30013345.
107. Yan S, Na J, Liu X, Wu P. Different targeting ligands mediated drug delivery systems for tumor therapy. Pharmaceutics. 2024;16(2):248. doi: 10.3390/pharmaceutics16020248, PMID 38399302.
108. Ates HC, Roberts JA, Lipman J, Cass AE, Urban GA, Dincer C. On site therapeutic drug monitoring. Trends Biotechnol. 2020;38(11):1262-77. doi: 10.1016/j.tibtech.2020.03.001, PMID 33058758.
109. Yuan D, He H, Wu Y, Fan J, Cao Y. Physiologically based pharmacokinetic modeling of nanoparticles. J Pharm Sci. 2019;108(1):58-72. doi: 10.1016/j.xphs.2018.10.037, PMID 30385282.
110. Le AD, Wearing HJ, Li D. Streamlining physiologically based pharmacokinetic model design for intravenous delivery of nanoparticle drugs. CPT Pharmacometrics Syst Pharmacol. 2022;11(4):409-24. doi: 10.1002/psp4.12762, PMID 35045205.
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