Author(s):
Suraj M. Patil, Amol R. Pawar, Pankaj S. Patil, Vikas V. Patil
Email(s):
sp129794@gmail.com
DOI:
10.52711/0974-4150.2026.00052 
Address:
Suraj M. Patil1*, Amol R. Pawar1,2, Pankaj S. Patil1, Vikas V. Patil1
1Department of Quality Assurance, Kisan Vidya Prasarak Sanstha’s Institute of Pharmaceutical Education, Boradi 425428, Maharashtra, India.
2Research Scholar, Sankalchand Patel University, Visnagar 384315, Gujarat, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 4,
Year - 2026
ABSTRACT:
Nanomedicine represents a rapidly evolving discipline that exploits the unique physicochemical behaviour of matter at the nanoscale to enable improved diagnosis, prevention and treatment of disease. Engineered carriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and metallic nanostructures can enhance aqueous solubility, prolong systemic circulation, reduce off-target toxicity and enable site-specific delivery of therapeutic payloads. However, the same nanoscale features that confer these advantages also introduce considerable analytical complexity: product behaviour in vivo depends not only on the molecular structure of the drug but also on the size distribution, surface charge, morphology, crystallinity and protein-corona profile of the carrier. Robust quality control is therefore essential to translate these systems from bench to clinic in a safe and reproducible manner. This review summarises the principal classes of nanocarriers and the critical quality attributes (CQAs) that govern their performance, including particle size and polydispersity index, zeta potential, surface chemistry, drug loading, entrapment efficiency, in vitro release kinetics and physicochemical stability. The role and complementary nature of modern analytical techniques such as dynamic light scattering, nanoparticle tracking analysis, electron and atomic-force microscopy, ultraviolet–visible and Fourier-transform infrared spectroscopy, high-performance liquid chromatography, differential scanning calorimetry, X-ray diffraction, Raman spectroscopy and inductively coupled plasma mass spectrometry are critically appraised. Regulatory expectations from the U.S. Food and Drug Administration, the European Medicines Agency and the International Council for Harmonisation, together with the Quality-by-Design framework, are discussed alongside emerging challenges such as protein-corona variability, blood–brain barrier translocation and harmonisation of release testing. The review concludes with future perspectives on artificial-intelligence-assisted characterisation, microfluidic in-line monitoring and standardised reference materials for nanomedicine.
Cite this article:
Suraj M. Patil, Amol R. Pawar, Pankaj S. Patil, Vikas V. Patil. Analytical Techniques for Quality Control of Nanomedicines: A Comprehensive Review. Asian Journal of Research in Chemistry.2026; 19(4):335-6. doi: 10.52711/0974-4150.2026.00052
Cite(Electronic):
Suraj M. Patil, Amol R. Pawar, Pankaj S. Patil, Vikas V. Patil. Analytical Techniques for Quality Control of Nanomedicines: A Comprehensive Review. Asian Journal of Research in Chemistry.2026; 19(4):335-6. doi: 10.52711/0974-4150.2026.00052 Available on: https://ajrconline.org/AbstractView.aspx?PID=2026-19-4-9
11. REFERENCES:
1. Freitas RA Jr. What is nanomedicine? Nanomedicine. 2005;1(1):2–9. doi: 10.1016/j.nano.2004.11.003.
2. Bayda S, Adeel M, Tuccinardi T, Cordani M, Rizzolio F. The history of nanoscience and nanotechnology: from chemical–physical applications to nanomedicine. Molecules. 2020;25(1):112. doi:10.3390/molecules25010112.
3. Soares S, Sousa J, Pais A, Vitorino C. Nanomedicine: principles, properties, and regulatory issues. Front Chem. 2018; 6:360. doi:10.3389/fchem.2018.00360.
4. Anselmo AC, Mitragotri S. Nanoparticles in the clinic: an update. Bioeng Transl Med. 2019;4(3):e10143. doi:10.1002/btm2.10143.
5. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2021; 20(2): 101–124. doi:10.1038/s41573-020-0090-8.
6. Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021; 6(12): 1078–1094. doi:10.1038/s41578-021-00358-0.
7. Akinc A, Maier MA, Manoharan M, Fitzgerald K, Jayaraman M, Barros S, et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat Nanotechnol. 2019; 14(12): 1084–1087. doi:10.1038/s41565-019-0591-y.
8. Schoenmaker L, Witzigmann D, Kulkarni JA, Verbeke R, Kersten G, Jiskoot W, et al. mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability. Int J Pharm. 2021; 601:120586. doi: 10.1016/j.ijpharm.2021.120586.
9. Caracciolo G, Farokhzad OC, Mahmoudi M. Biological identity of nanoparticles in vivo: clinical implications of the protein corona. Trends Biotechnol. 2017; 35(3): 257–264. doi: 10.1016/j.tibtech.2016.08.011.
10. Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid nanoparticles—from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano. 2021; 15(11): 16982–17015. doi:10.1021/acsnano.1c04996.
11. Lin PC, Lin S, Wang PC, Sridhar R. Techniques for physicochemical characterization of nanomaterials. Biotechnol Adv. 2014;32(4):711–726. doi: 10.1016/j.biotechadv.2013.11.006.
12. Mourdikoudis S, Pallares RM, Thanh NTK. Characterization techniques for nanoparticles: comparison and complementarity upon studying nanoparticle properties. Nanoscale. 2018; 10(27): 12871–12934. doi:10.1039/c8nr02278j.
13. Sapsford KE, Tyner KM, Dair BJ, Deschamps JR, Medintz IL. Analyzing nanomaterial bioconjugates: a review of current and emerging purification and characterization techniques. Anal Chem. 2011; 83(12): 4453–4488. doi:10.1021/ac200853a.
14. U.S. Food and Drug Administration. Drug products, including biological products, that contain nanomaterials: guidance for industry. Silver Spring (MD): FDA; 2022.
15. European Medicines Agency. Reflection paper on the data requirements for intravenous liposomal products developed with reference to an innovator liposomal product. London: EMA; 2013.
16. International Council for Harmonisation. ICH Q8(R2) Pharmaceutical Development. Geneva: ICH; 2009.
17. Caputo F, Clogston J, Calzolai L, Rosslein M, Prina-Mello A. Measuring particle size distribution of nanoparticle enabled medicinal products, the joint view of EUNCL and NCI-NCL. J Control Release. 2019; 299: 31–43. doi: 10.1016/j.jconrel.2019.02.030.
18. Crist RM, Grossman JH, Patri AK, Stern ST, Dobrovolskaia MA, Adiseshaiah PP, et al. Common pitfalls in nanotechnology: lessons learned from NCI’s Nanotechnology Characterization Laboratory. Integr Biol. 2013;5(1):66–73. doi:10.1039/c2ib20117h.
19. Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018; 16(1): 71. doi:10.1186/s12951-018-0392-8.
20. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015; 10: 975–999. doi:10.2147/IJN.S68861.
21. Nsairat H, Khater D, Sayed U, Odeh F, Al Bawab A, Alshaer W. Liposomes: structure, composition, types, and clinical applications. Heliyon. 2022; 8(5): e09394. doi: 10.1016/j.heliyon. 2022.e09394.
22. 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.
23. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48. doi: 10.1016/j.addr.2012.09.037.
24. Zielinska A, Carreiró F, Oliveira AM, Neves A, Pires B, Venkatesh DN, et al. Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules. 2020; 25(16): 3731. doi:10.3390/molecules25163731.
25. Begines B, Ortiz T, Perez-Aranda M, Martínez G, Merinero M, Argüelles-Arias F, et al. Polymeric nanoparticles for drug delivery: recent developments and analysis. Nanomaterials. 2020; 10(7): 1403. doi:10.3390/nano10071403.
26. El-Hammadi MM, Arias JL. An update on liposomes in drug delivery: a patent review (2014–2018). Expert Opin Ther Pat. 2019; 29(11): 891–907. doi:10.1080/13543776.2019.1679767.
27. Cano A, Ettcheto M, Espina M, Lopez-Machado A, Cajal Y, Rabanal F, et al. State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections. J Nanobiotechnology. 2020; 18(1): 156. doi:10.1186/s12951-020-00714-2.
28. Mishra V, Bansal KK, Verma A, Yadav N, Thakur S, Sudhakar K, et al. Solid lipid nanoparticles: emerging colloidal nano drug delivery systems. Pharmaceutics. 2018; 10(4): 191. doi:10.3390/pharmaceutics10040191.
29. Duong VA, Nguyen TT, Maeng HJ. Preparation of solid lipid nanoparticles and nanostructured lipid carriers for drug delivery and the effects of preparation parameters of solvent injection method. Molecules. 2020; 25(20): 4781. doi:10.3390/molecules25204781.
30. Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018; 13(4): 288–303. doi:10.4103/1735-5362.235156.
31. Khosa A, Reddi S, Saha RN. Nanostructured lipid carriers for site-specific drug delivery. Biomed Pharmacother. 2018; 103: 598–613. doi: 10.1016/j.biopha.2018.04.055.
32. 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): 143–161. doi: 10.1016/j.nano.2015.09.004.
33. Yaqoob AA, Ahmad H, Parveen T, Ahmad A, Oves M, Ismail IM, et al. Recent advances in metal decorated nanomaterials and their various biological applications: a review. Front Chem. 2020; 8: 341. doi:10.3389/fchem.2020.00341.
34. Sharma A, Goyal AK, Rath G. Recent advances in metal nanoparticles in cancer therapy. J Drug Target. 2018; 26(8): 617–632. doi:10.1080/1061186X.2017.1400553.
35. Mauricio MD, Guerra-Ojeda S, Marchio P, Valles SL, Aldasoro M, Escribano-Lopez I, et al. Nanoparticles in medicine: a focus on vascular oxidative stress. Oxid Med Cell Longev. 2018; 2018: 6231482. doi:10.1155/2018/6231482.
36. International Council for Harmonisation. ICH Q8(R2): Pharmaceutical Development. Geneva: ICH; 2009.
37. Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, et al. Understanding pharmaceutical quality by design. AAPS J. 2014; 16(4): 771–783. doi:10.1208/s12248-014-9598-3.
38. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015; 33(9): 941–951. doi:10.1038/nbt.3330.
39. Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine. 2016; 11(6): 673–692. doi:10.2217/nnm.16.5.
40. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018; 10(2): 57. doi:10.3390/pharmaceutics10020057.
41. Bhattacharjee S. DLS and zeta potential—what they are and what they are not? J Control Release. 2016; 235: 337–351. doi: 10.1016/j.jconrel.2016.06.017.
42. Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol. 2011; 697: 63–70. doi:10.1007/978-1-60327-198-1_6.
43. Frohlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012; 7: 5577–5591. doi:10.2147/IJN.S36111.
44. Truong NP, Whittaker MR, Mak CW, Davis TP. The importance of nanoparticle shape in cancer drug delivery. Expert Opin Drug Deliv. 2015;12(1):129–142. doi:10.1517/17425247.2014.950564.
45. Patel V, Sharma OP, Mehta T. Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery. Expert Opin Drug Deliv. 2018; 15(4): 351–368. doi:10.1080/17425247.2018.1444025.
46. D’Souza S. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharm. 2014; 2014: 304757. doi:10.1155/2014/304757.
47. Mehnert W, Mader K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2012; 64: 83–101. doi: 10.1016/j.addr.2012.09.021.
48. Stetefeld J, McKenna SA, Patel TR. Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys Rev. 2016; 8(4): 409–427. doi:10.1007/s12551-016-0218-6.
49. Caputo F, Vogel R, Savage J, Vella G, Law A, Della Camera G, et al. Measuring particle size distribution and mass concentration of nanoplastics and microplastics: addressing some analytical challenges in the sub-micron size range. J Colloid Interface Sci. 2021; 588: 401–417. doi: 10.1016/j.jcis.2020.12.039.
50. Filipe V, Hawe A, Jiskoot W. Critical evaluation of nanoparticle tracking analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010; 27(5): 796–810. doi:10.1007/s11095-010-0073-2.
51. Bachurski D, Schuldner M, Nguyen PH, Malz A, Reiners KS, Grenzi PC, et al. Extracellular vesicle measurements with nanoparticle tracking analysis—an accuracy and repeatability comparison between NanoSight NS300 and ZetaView. J Extracell Vesicles. 2019; 8(1): 1596016. doi:10.1080/20013078.2019.1596016.
52. Lowry GV, Hill RJ, Harper S, Rawle AF, Hendren CO, Klaessig F, et al. Guidance to improve the scientific value of zeta-potential measurements in nanoEHS. Environ Sci Nano. 2016; 3(5): 953–965. doi:10.1039/c6en00136j.
53. Ali A, Zafar H, Zia M, ul Haq I, Phull AR, Ali JS, et al. Synthesis, characterization, applications, and challenges of iron oxide nanoparticles. Nanotechnol Sci Appl. 2016; 9: 49–67. doi:10.2147/NSA.S99986.
54. Brink HJ, van Steensel MAM, Bremer E, Krieg T, Reijnders M, van der Marel GA, et al. Cryo-EM of nanoparticle–drug formulations: structural insight at near-physiological conditions. Adv Drug Deliv Rev. 2022; 188: 114457. doi: 10.1016/j.addr.2022.114457.
55. Eygeris Y, Gupta M, Kim J, Sahay G. Chemistry of lipid nanoparticles for RNA delivery. Acc Chem Res. 2022; 55(1): 2–12. doi: 10.1021/acs.accounts.1c00544.
56. Ruozi B, Belletti D, Tombesi A, Tosi G, Bondioli L, Forni F, et al. AFM, ESEM, TEM, and CLSM in liposomal characterization: a comparative study. Int J Nanomedicine. 2011; 6: 557–563. doi:10.2147/IJN.S14615.
57. Beck-Broichsitter M, Schmehl T, Gessler T, Seeger W, Kissel T. Development of a biodegradable nanoparticle platform for sildenafil: formulation optimization by factorial design analysis combined with application of charge-modified branched polyesters. J Control Release. 2012; 157(3): 469–477. doi: 10.1016/j.jconrel.2011.09.058.
58. Mohamed MA, Jaafar J, Ismail AF, Othman MHD, Rahman MA. Fourier Transform Infrared (FTIR) Spectroscopy. In: Membrane Characterization. Amsterdam: Elsevier; 2017. p. 3–29. doi:10.1016/B978-0-444-63776-5.00001-2.
59. ICH Harmonised Guideline. Q14: Analytical procedure development. Geneva: ICH; 2023.
60. Bunjes H, Unruh T. Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv Drug Deliv Rev. 2007; 59(6): 379–402. doi: 10.1016/j.addr.2007.04.013.
61. Yu D, Zhu X, Williams GR, Branford-White CJ, Wang X, Zhu LM. Drug-loaded amorphous solid dispersion in polymeric nanoparticles: a strategy to enhance dissolution. Drug Discov Today. 2018; 23(2): 443–452. doi: 10.1016/j.drudis.2017.10.022.
62. Cialla-May D, Schmitt M, Popp J. Theoretical principles of Raman spectroscopy. Phys Sci Rev. 2019;4(6):20170040. doi:10.1515/psr-2017-0040.
63. Laborda F, Bolea E, Cepriá G, Jiménez MS, Pérez-Arantegui J, Castillo JR. Detection, characterization and quantification of inorganic engineered nanomaterials: a review of techniques and methodological approaches for the analysis of complex samples. Anal Chim Acta. 2016; 904:10–32. doi: 10.1016/j.aca.2015.11.008.
64. U.S. Food and Drug Administration. Liposome drug products: chemistry, manufacturing, and controls; human pharmacokinetics and bioavailability; and labeling documentation. Silver Spring (MD): FDA; 2018.
65. European Medicines Agency. Reflection paper on the data requirements for intravenous iron-based nano-colloidal products developed with reference to an innovator medicinal product. London: EMA; 2015.
66. U.S. Food and Drug Administration. Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA. Silver Spring (MD): FDA; 2021.
67. European Medicines Agency. Joint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products. London: EMA; 2014.
68. International Council for Harmonisation. ICH Q9: Quality Risk Management. Geneva: ICH; 2005.
69. International Council for Harmonisation. ICH Q10: Pharmaceutical Quality System. Geneva: ICH; 2008.
70. Bastogne T. Quality-by-design of nanopharmaceuticals—a state of the art. Nanomedicine. 2017; 13(7): 2151–2157. doi: 10.1016/j.nano.2017.05.014.
71. International Council for Harmonisation. ICH Q1A(R2): Stability testing of new drug substances and products. Geneva: ICH; 2003.
72. Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol. 2013; 8(10): 772–781. doi:10.1038/nnano.2013.181.
73. Corbo C, Molinaro R, Parodi A, Toledano Furman NE, Salvatore F, Tasciotti E. The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery. Nanomedicine. 2016; 11(1): 81–100. doi:10.2217/nnm.15.188.
74. Pardridge WM. Drug transport across the blood–brain barrier. J Cereb Blood Flow Metab. 2012; 32(11): 1959–1972. doi:10.1038/jcbfm.2012.126.
75. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010; 37(1): 13–25. doi: 10.1016/j.nbd.2009.07.030.
76. Saraiva C, Praca C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: overcoming blood–brain barrier to treat neurodegenerative diseases. J Control Release. 2016; 235:34–47. doi: 10.1016/j.jconrel.2016.05.044.
77. Illum L. Nasal drug delivery: new developments and strategies. Drug Discov Today. 2002; 7(23): 1184–1189. doi:10.1016/s1359-6446(02)02529-1.
78. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014; 66: 2–25. doi: 10.1016/j.addr.2013.11.009.
79. Crist RM, Dasa SSK, Liu CH, Clogston JD, Dobrovolskaia MA, Stern ST. Challenges in the development of nanoparticle-based imaging agents: characterization and regulatory considerations. WIREs Nanomed Nanobiotechnol. 2021; 13(3): e1665. doi:10.1002/wnan.1665.
80. Cho EJ, Holback H, Liu KC, Abouelmagd SA, Park J, Yeo Y. Nanoparticle characterization: State of the art, challenges, and emerging technologies. Mol Pharm. 2013; 10(6): 2093–2110. doi:10.1021/mp300697h.