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Advancements in nanoscale delivery systems: optimizing intermolecular interactions for superior drug encapsulation and precision release

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Abstract

Nanoscale preparations, such as nanoparticles, micelles, and liposomes, are increasingly recognized in pharmaceutical technology for their high capability in tailoring the pharmacokinetics of the encapsulated drug within the body. These preparations have great potential in extending drug half-life, reducing dosing frequency, mitigating drug side effects, and enhancing drug efficacy. Consequently, nanoscale preparations offer promising prospects for the treatment of metabolic disorders, malignant tumors, and various chronic diseases. Nevertheless, the complete clinical potential of nanoscale preparations remains untapped due to the challenges associated with low drug loading degrees and insufficient control over drug release. In this review, we comprehensively summarize the vital role of intermolecular interactions in enhancing encapsulation and controlling drug release within nanoscale delivery systems. Our analysis critically evaluates the characteristics of common intermolecular interactions and elucidates the techniques employed to assess them. Moreover, we highlight the significant potential of intermolecular interactions in clinical translation, particularly in the screening and optimization of preparation prescriptions. By attaining a deeper understanding of intermolecular interaction properties and mechanisms, we can adopt a more rational approach to designing drug carriers, leading to substantial advancements in the application and clinical transformation of nanoscale preparations. Moving forward, continued research in this field offers exciting prospects for unlocking the full clinical potential of nanoscale preparations and revolutionizing the field of drug delivery.

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References

  1. Zhang C, Yan L, Wang X, Zhu S, Chen C, Gu Z, Zhao Y. Progress, challenges, and future of nanomedicine. Nano Today. 2020;35: 101008.

    Article  CAS  Google Scholar 

  2. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discovery. 2020;20:101–24.

    Article  PubMed  Google Scholar 

  3. Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2016;17:20–37.

    Article  PubMed  PubMed Central  Google Scholar 

  4. He H, Liu L, Morin EE, Liu M, Schwendeman A. Survey of clinical translation of cancer nanomedicines—lessons learned from successes and failures. Acc Chem Res. 2019;52:2445–61.

    Article  CAS  PubMed  Google Scholar 

  5. Grimaldi N, Andrade F, Segovia N, Ferrer-Tasies L, Sala S, Veciana J, Ventosa N. Lipid-based nanovesicles for nanomedicine. Chem Soc Rev. 2016;45:6520–45.

    Article  CAS  PubMed  Google Scholar 

  6. Gawne PJ, Ferreira M, Papaluca M, Grimm J, Decuzzi P. New opportunities and old challenges in the clinical translation of nanotheranostics. Nat Rev Mater. 2023;8:783–98.

    Article  Google Scholar 

  7. Hare JI, Lammers T, Ashford MB, Puri S, Storm G, Barry ST. Challenges and strategies in anti-cancer nanomedicine development: An industry perspective. Adv Drug Deliv Rev. 2017;108:25–38.

    Article  CAS  PubMed  Google Scholar 

  8. Gao S, Yang X, Xu J, Qiu N, Zhai G. Nanotechnology for Boosting Cancer Immunotherapy and Remodeling Tumor Microenvironment: The Horizons in Cancer Treatment. ACS Nano. 2021;15:12567–603.

    Article  CAS  PubMed  Google Scholar 

  9. Tzeng SY, McHugh KJ, Behrens AM, Rose S, Sugarman JL, Ferber S, Langer R, Jaklenec A. Stabilized single-injection inactivated polio vaccine elicits a strong neutralizing immune response. Proc Natl Acad Sci. 2018;115:E5269–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McHugh KJ, Nguyen TD, Linehan AR, Yang D, Behrens AM, Rose S, Tochka ZL, Tzeng SY, Norman JJ, Anselmo AC. Fabrication of fillable microparticles and other complex 3D microstructures. Science. 2017;357:1138–42.

    Article  CAS  PubMed  Google Scholar 

  11. Caudill C, Perry JL, Iliadis K, Tessema AT, Lee BJ, Mecham BS, Tian S, DeSimone JM. Transdermal vaccination via 3D-printed microneedles induces potent humoral and cellular immunity. Proc Natl Acad Sci. 2021;118: e2102595118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guidolin K, Zheng G. Nanomedicines Lost in Translation. ACS Nano. 2019;13:13620–6.

    Article  CAS  PubMed  Google Scholar 

  13. Liu D, Zhang H, Fontana F, Hirvonen JT, Santos HA. Current developments and applications of microfluidic technology toward clinical translation of nanomedicines. Adv Drug Deliv Rev. 2018;128:54–83.

    Article  CAS  PubMed  Google Scholar 

  14. Coty J-B, Vauthier C. Characterization of nanomedicines: A reflection on a field under construction needed for clinical translation success. J Control Release. 2018;275:254–68.

    Article  CAS  PubMed  Google Scholar 

  15. Li Y, Yang L. Driving forces for drug loading in drug carriers. J Microencapsul. 2015;32:255–72.

    Article  PubMed  Google Scholar 

  16. Wolfram J, Ferrari M. Clinical cancer nanomedicine. Nano Today. 2019;25:85–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Doshi N, Mitragotri S. Designer Biomaterials for Nanomedicine. Adv Func Mater. 2009;19:3843–54.

    Article  CAS  Google Scholar 

  18. Zhang Z, Feng S-S. The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)–tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials. 2006;27:4025–33.

    Article  CAS  PubMed  Google Scholar 

  19. Wang G, Xu W, Liu Y, Fu N. Ultrasensitive detection and high-contrast bioimaging of Hg2+ using monothiosquaraine-based fluorescent probe via hydrogen bond promoted desulfurization. Microchem J. 2022;179: 107481.

    Article  CAS  Google Scholar 

  20. Grabowski SJ. What Is the Covalency of Hydrogen Bonding? Chem Rev. 2011;111:2597–625.

    Article  CAS  PubMed  Google Scholar 

  21. Afonin AV, Vashchenko AV, Sigalov MV. Estimating the energy of intramolecular hydrogen bonds from1H NMR and QTAIM calculations. Org Biomol Chem. 2016;14:11199–211.

    Article  CAS  PubMed  Google Scholar 

  22. Hunt PA, Ashworth CR, Matthews RP. Hydrogen bonding in ionic liquids. Chem Soc Rev. 2015;44:1257–88.

    Article  CAS  PubMed  Google Scholar 

  23. He Y, Zhu B, Inoue Y. Hydrogen bonds in polymer blends. Prog Polym Sci. 2004;29:1021–51.

    Article  CAS  Google Scholar 

  24. Ahmed I, Jhung SH. Applications of metal-organic frameworks in adsorption/separation processes via hydrogen bonding interactions. Chem Eng J. 2017;310:197–215.

    Article  CAS  Google Scholar 

  25. Bhadra D, Bhadra S, Jain S, Jain NK. A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int J Pharm. 2003;257:111–24.

    Article  CAS  PubMed  Google Scholar 

  26. Kim SH, Tan JPK, Nederberg F, Fukushima K, Colson J, Yang C, Nelson A, Yang Y-Y, Hedrick JL. Hydrogen bonding-enhanced micelle assemblies for drug delivery. Biomaterials. 2010;31:8063–71.

    Article  CAS  PubMed  Google Scholar 

  27. Lee J, Cho EC, Cho K. Incorporation and release behavior of hydrophobic drug in functionalized poly(d, l-lactide)-block–poly(ethylene oxide) micelles. J Control Release. 2004;94:323–35.

    Article  CAS  PubMed  Google Scholar 

  28. Luxenhofer R, Schulz A, Roques C, Li S, Bronich TK, Batrakova EV, Jordan R, Kabanov AV. Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs. Biomaterials. 2010;31:4972–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chang L, Deng L, Wang W, Lv Z, Hu F, Dong A, Zhang J. Poly(ethyleneglycol)-b-Poly(ε-caprolactone-co-γ-hydroxyl-ε- caprolactone) Bearing Pendant Hydroxyl Groups as Nanocarriers for Doxorubicin Delivery. Biomacromol. 2012;13:3301–10.

    Article  CAS  Google Scholar 

  30. Neelakandan C, Kyu T. Effects of genistein modification on miscibility and hydrogen bonding interactions in poly(amide)/poly(vinyl pyrrolidone) blends and membrane morphology development during coagulation. Polymer. 2010;51:5135–44.

    Article  CAS  Google Scholar 

  31. Sawada T, Fujita M. A single watson− crick G· C base pair in water: aqueous hydrogen bonds in hydrophobic cavities. J Am Chem Soc. 2010;132:7194–201.

    Article  CAS  PubMed  Google Scholar 

  32. Xiao F, Chen Z, Wei Z, Tian L. Hydrophobic interaction: a promising driving force for the biomedical applications of nucleic acids. Adv Sci. 2020;7:2001048.

    Article  CAS  Google Scholar 

  33. Gebbie MA, Smith AM, Dobbs HA, Warr GG, Banquy X, Valtiner M, Rutland MW, Israelachvili JN, Perkin S, Atkin R. Long range electrostatic forces in ionic liquids. Chem Commun. 2017;53:1214–24.

    Article  CAS  Google Scholar 

  34. Blum JS, Saltzman WM. High loading efficiency and tunable release of plasmid DNA encapsulated in submicron particles fabricated from PLGA conjugated with poly-L-lysine. J Control Release. 2008;129:66–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang P, Du C, Huang T, Hu S, Bai Y, Li C, Feng G, Gao Y, Li Z, Wang B, Hirvonen JT, Fan J, Santos HA, Liu D. Surface adsorption-mediated ultrahigh efficient peptide encapsulation with a precise ratiometric control for type 1 and 2 diabetic therapy. Small. 2022;18:2200449.

    Article  CAS  Google Scholar 

  36. Huo Q, Gao Y, Wu W, Hu S, Dong E, Zhang Y, Tian Y, Huang Y, Quan P, Liu D. Plugging the leak of nanoparticles by interfacial polymer adsorption enables an efficient protein and peptide encapsulation. Adv Funct Mater. 2023;34(6):2310146.

    Article  Google Scholar 

  37. Zhang P, Li C, Huang T, Bai Y, Quan P, Li W, Zhang Z, Zhang F, Liu Z, Wan B, Correia A, Zhang J, Wu X, Hirvonen JT, Santos HA, Fan J, Cai T, Liu D. Inhibiting phase transfer of protein nanoparticles by surface camouflage–a versatile and efficient protein encapsulation strategy. Nano Lett. 2021;21:9458–67.

    Article  CAS  PubMed  Google Scholar 

  38. Huo Q, Gao Y, Wu W, Hu S, Zhang Z, Li Z, Tian Y, Quan P, Li W, Liu D. Colloidal jamming by interfacial self-assembled polymers: a robust route for ultrahigh efficient encapsulation. Angew Chem Int Ed. 2022;61: e202208738.

    Article  CAS  Google Scholar 

  39. Zhang P, Liu Y, Feng G, Li C, Zhou J, Du C, Bai Y, Hu S, Huang T, Wang G, Quan P, Hirvonen J, Fan J, Santos HA, Liu D. Controlled interfacial polymer self-assembly coordinates ultrahigh drug loading and zero-order release in particles prepared under continuous flow. Adv Mater. 2023;35: e2211254.

    Article  PubMed  Google Scholar 

  40. Huo Q, Zhou J, Tang H, Wu W, Hu S, Dong E, Huang Y, Zhou Y, Gao Y, Bai Y, Liu D. Nanoparticle surface decoration mediated efficient protein and peptide co-encapsulation with precise ratiometric control for self-regulated drug release. Nanoscale. 2023;15:5063–73.

    Article  CAS  PubMed  Google Scholar 

  41. Huang T, Wang G, Shahbazi MA, Bai Y, Zhang J, Feng G, Asadian E, Ghorbani-Bidkorpeh F, Yang Z, Li Y, Huo Q, Liu Y, Liu D. Surface decoration of peptide nanoparticles enables efficient therapy toward osteoporosis and diabetes. Adv Func Mater. 2022;33:2210627.

    Article  Google Scholar 

  42. Muller P. Glossary of terms used in physical organic chemistry (IUPAC Recommendations 1994). Pure Appl Chem. 1994;66:1077–184.

    Article  Google Scholar 

  43. Hermann J, DiStasio RA, Tkatchenko A. First-principles models for van der waals interactions in molecules and materials: concepts, theory, and applications. Chem Rev. 2017;117:4714–58.

    Article  CAS  PubMed  Google Scholar 

  44. Mohammed AR, Weston N, Coombes AGA, Fitzgerald M, Perrie Y. Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability. Int J Pharm. 2004;285:23–34.

    Article  CAS  PubMed  Google Scholar 

  45. Hassanzadeh S, Khoee S, Firoozpour L. Effect of the copolymerized aromatic and unsaturated monomers on the affinity of drug-polyesters in the core-shell nanoparticles. Macromol Res. 2012;21:55–64.

    Article  Google Scholar 

  46. Israelachvili J, Pashley R. The hydrophobic interaction is long range, decaying exponentially with distance. Nature. 1982;300:341–2.

    Article  CAS  PubMed  Google Scholar 

  47. Meyer EE, Rosenberg KJ, Israelachvili J. Recent progress in understanding hydrophobic interactions. Proc Natl Acad Sci. 2006;103:15739–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chandler D. Interfaces and the driving force of hydrophobic assembly. Nature. 2005;437:640–7.

    Article  CAS  PubMed  Google Scholar 

  49. Silvera Batista CA, Larson RG, Kotov NA. Nonadditivity of nanoparticle interactions. Science. 2015;350:1242477.

    Article  Google Scholar 

  50. Bogunia M, Makowski M. Influence of ionic strength on hydrophobic interactions in water: dependence on solute size and shape. J Phys Chem B. 2020;124:10326–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dutta P, Dey J, Perumal V, Mandal M. Amino acid based amphiphilic copolymer micelles as carriers of non-steroidal anti-inflammatory drugs: Solubilization, in vitro release and biological evaluation. Int J Pharm. 2011;407:207–16.

    Article  CAS  PubMed  Google Scholar 

  52. Wang D, Su Y, Jin C, Zhu B, Pang Y, Zhu L, Liu J, Tu C, Yan D, Zhu X. Supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases for drug delivery. Biomacromol. 2011;12:1370–9.

    Article  CAS  Google Scholar 

  53. Acevedo-Guevara L, Nieto-Suaza L, Sanchez LT, Pinzon MI, Villa CC. Development of native and modified banana starch nanoparticles as vehicles for curcumin. Int J Biol Macromol. 2018;111:498–504.

    Article  CAS  PubMed  Google Scholar 

  54. Ke X, Tang H, Mao H-Q. Effective encapsulation of curcumin in nanoparticles enabled by hydrogen bonding using flash nanocomplexation. Int J Pharm. 2019;564:273–80.

    Article  CAS  PubMed  Google Scholar 

  55. Cheng C-C, Sun Y-T, Lee A-W, Huang S-Y, Fan W-L, Chiao Y-H, Chiu C-W, Lai J-Y. Hydrogen-bonded supramolecular micelle-mediated drug delivery enhances the efficacy and safety of cancer chemotherapy. Polym Chem. 2020;11:2791–8.

    Article  CAS  Google Scholar 

  56. Wang J, Liu LG, Jiao W-Q, Yang H, Liu J, Liu D. Phenylboronic acid-conjugated chitosan nanoparticles for high loading and efficient delivery of curcumin. Carbohyd Polym. 2021;256: 117497.

    Article  CAS  Google Scholar 

  57. Chang B, Guo J, Liu C, Qian J, Yang W. Surface functionalization of magnetic mesoporous silica nanoparticles for controlled drug release. J Mater Chem. 2010;20:9941–7.

    Article  CAS  Google Scholar 

  58. Li P, Wang Y, Peng Z, She F, Kong L. Development of chitosan nanoparticles as drug delivery systems for 5-fluorouracil and leucovorin blends. Carbohyd Polym. 2011;85:698–704.

    Article  CAS  Google Scholar 

  59. Lv S, Li M, Tang Z, Song W, Sun H, Liu H, Chen X. Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy. Acta Biomater. 2013;9:9330–42.

    Article  CAS  PubMed  Google Scholar 

  60. Xiao H, Stefanick JF, Jia X, Jing X, Kiziltepe T, Zhang Y, Bilgicer B. Micellar nanoparticle formation via electrostatic interactions for delivering multinuclear platinum(II) drugs. Chem Commun. 2013;49:4809–11.

    Article  CAS  Google Scholar 

  61. Croissant JG, Zhang D, Alsaiari S, Lu J, Deng L, Tamanoi F, AlMalik AM, Zink JI, Khashab NM. Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging. J Control Release. 2016;229:183–91.

    Article  CAS  PubMed  Google Scholar 

  62. Huang D, Zhou Y, Xiang Y, Shu M, Chen H, Yang B, Liao X. Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH-sensitive drug delivery carriers. Polym Int. 2018;67:1186–93.

    Article  CAS  Google Scholar 

  63. Kubo S, Kadla JF. The formation of strong intermolecular interactions in immiscible blends of poly (vinyl alcohol)(PVA) and lignin. Biomacromol. 2003;4:561–7.

    Article  CAS  Google Scholar 

  64. Lin S-Y, Chen K-S, Liang R-C. Thermal micro ATR/FT-IR spectroscopic system for quantitative study of the molecular structure of poly (N-isopropylacrylamide) in water. Polymer. 1999;40:2619–24.

    Article  CAS  Google Scholar 

  65. Xie B, Liu R, Han Y, Xu H, Jiang C, Wu H, Wang H. The polarized Raman spectra of N-methylpyrrolidone-an effective method for determination of intermolecular interaction and H-bond formation. Spectrochim Acta Part A Mol Biomol Spectrosc. 2023;284: 121808.

    Article  CAS  Google Scholar 

  66. Giacomelli C, Schmidt V, Borsali R. Specific interactions improve the loading capacity of block copolymer micelles in aqueous media. Langmuir. 2007;23:6947–55.

    Article  CAS  PubMed  Google Scholar 

  67. Shi Y, van Steenbergen MJ, Teunissen EA, Novo L, Gradmann S, Baldus M, van Nostrum CF, Hennink WE. Π–Π Stacking increases the stability and loading capacity of thermosensitive polymeric micelles for chemotherapeutic drugs. Biomacromolecules. 2023;14(6):1826–37.

    Article  Google Scholar 

  68. Azevedo JR, Sizilio RH, Brito MB, Costa AMB, Serafini MR, Araújo AAS, Santos MRV, Lira AAM, Nunes RS. Physical and chemical characterization insulin-loaded chitosan-TPP nanoparticles. J Therm Anal Calorim. 2011;106:685–9.

    Article  CAS  Google Scholar 

  69. Bastos M, Abian O, Johnson CM, Ferreira-da-Silva F, Vega S, Jimenez-Alesanco A, Ortega-Alarcon D, Velazquez-Campoy A. Isothermal titration calorimetry. Nature Reviews Methods Primers. 2023;3:17.

    Article  CAS  Google Scholar 

  70. Velázquez-Campoy A, Ohtaka H, Nezami A, Muzammil S, Freire E. Isothermal Titration Calorimetry. Curr Protoc Cell Biol. 2004;23(1):17-8.24.

    Article  Google Scholar 

  71. Lima Cavalcanti ID, Xavier Junior FH, Santos Magalhães NS, Lira Nogueira MC, dB,. Isothermal titration calorimetry (ITC) as a promising tool in pharmaceutical nanotechnology. Int J Pharm. 2023;641:123063.

    Article  CAS  PubMed  Google Scholar 

  72. Greytak AB, Abiodun SL, Burrell JM, Cook EN, Jayaweera NP, Islam MM, Shaker AE. Thermodynamics of nanocrystal–ligand binding through isothermal titration calorimetry. Chem Commun. 2022;58:13037–58.

    Article  CAS  Google Scholar 

  73. Michaud-Agrawal N, Denning EJ, Woolf TB, Beckstein O. MDAnalysis: A toolkit for the analysis of molecular dynamics simulations. J Comput Chem. 2011;32:2319–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hansson T, Oostenbrink C, van Gunsteren W. Molecular dynamics simulations. Curr Opin Struct Biol. 2002;12:190–6.

    Article  CAS  PubMed  Google Scholar 

  75. Yani Y, Kanaujia P, Chow PS, Tan RBH. Effect of API-Polymer Miscibility and Interaction on the Stabilization of Amorphous Solid Dispersion: A Molecular Simulation Study. Ind Eng Chem Res. 2017;56:12698–707.

    Article  CAS  Google Scholar 

  76. Yahyaei M, Mehrnejad F, Naderi-manesh H, Rezayan AH. Protein adsorption onto polysaccharides: Comparison of chitosan and chitin polymers. Carbohyd Polym. 2018;191:191–7.

    Article  CAS  Google Scholar 

  77. von Ranke NL, Castro HC, Rodrigues CR. Molecular modelling and dynamics simulations of single-wall carbon nanotube as a drug carrier: New insights into the drug-loading process. J Mol Graph Model. 2022;113:108145.

    Article  Google Scholar 

  78. Roosta S, Nikkhah SJ, Sabzali M, Hashemianzadeh SM. Molecular dynamics simulation study of boron-nitride nanotubes as a drug carrier: from encapsulation to releasing. RSC Adv. 2016;6:9344–51.

    Article  CAS  Google Scholar 

  79. Karnati KR, Wang Y. Understanding the co-loading and releasing of doxorubicin and paclitaxel using chitosan functionalized single-walled carbon nanotubes by molecular dynamics simulations. Phys Chem Chem Phys. 2018;20:9389–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tohidifar L, Strodel B. Molecular dynamics studies for enhancing the anticancer drug efficacy: Toward designing a new carbon nanotube-based paclitaxel delivery system. J Mol Liq. 2021;323: 114638.

    Article  CAS  Google Scholar 

  81. Arabian T, Amjad-Iranagh S, Halladj R. Molecular dynamics simulation study of doxorubicin adsorption on functionalized carbon nanotubes with folic acid and tryptophan. Sci Rep. 2021;11:24210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. López CA, Sovova Z, van Eerden FJ, de Vries AH, Marrink SJ. Martini force field parameters for glycolipids. J Chem Theory Comput. 2013;9:1694–708.

    Article  PubMed  Google Scholar 

  83. Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, De Vries AH. The MARTINI force field: coarse grained model for biomolecular simulations. J Phys Chem B. 2007;111:7812–24.

    Article  CAS  PubMed  Google Scholar 

  84. Voth GA. Coarse-graining of condensed phase and biomolecular systems. CRC Press; 2008.

    Book  Google Scholar 

  85. Conte M, Fiorillo L, Bianco S, Chiariello AM, Esposito A, Nicodemi M. Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation. Nat Commun. 2020;11:3289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Jing H, Wang Y, Desai PR, Ramamurthi KS, Das S. Formation and properties of a self-assembled nanoparticle-supported lipid bilayer probed through molecular dynamics simulations. Langmuir. 2020;36:5524–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Larsen AH. Molecular dynamics simulations of curved lipid membranes. Int J Mol Sci. 2022;23:8098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Cheng Y, Yuan S. Emulsification of surfactant on oil droplets by molecular dynamics simulation. Molecules. 2020;25:3008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hashemzadeh H, Javadi H, Darvishi MH. Study of structural stability and formation mechanisms in DSPC and DPSM liposomes: a coarse-grained molecular dynamics simulation. Sci Rep. 2020;10:1837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Brunk NE, Uchida M, Lee B, Fukuto M, Yang L, Douglas T, Jadhao V. Linker-mediated assembly of virus-like particles into ordered arrays via electrostatic control. ACS Appl Bio Mater. 2019;2:2192–201.

    Article  CAS  PubMed  Google Scholar 

  91. Lübtow MM, Haider MS, Kirsch M, Klisch S, Luxenhofer R. Like dissolves like? a comprehensive evaluation of partial solubility parameters to predict polymer-drug compatibility in ultrahigh drug-loaded polymer micelles. Biomacromol. 2019;20:3041–56.

    Article  Google Scholar 

  92. Williams LL, Rubin JB, Edwards H. Calculation of Hansen solubility parameter values for a range of pressure and temperature conditions, including the supercritical fluid region. Ind Eng Chem Res. 2004;43:4967–72.

    Article  CAS  Google Scholar 

  93. Mohammad MA, Alhalaweh A, Velaga SP. Hansen solubility parameter as a tool to predict cocrystal formation. Int J Pharm. 2011;407:63–71.

    Article  CAS  PubMed  Google Scholar 

  94. Turpin ER, Taresco V, Al-Hachami WA, Booth J, Treacher K, Tomasi S, Alexander C, Burley J, Laughton CA, Garnett MC. In silico screening for solid dispersions: the trouble with solubility parameters and χFH. Mol Pharm. 2018;15:4654–67.

    Article  CAS  PubMed  Google Scholar 

  95. Hu C, Yan Q, Zhang Y, Yan H. Influence mechanism of drug-polymer compatibility on humidity stability of crystalline solid dispersion. Pharmaceuticals. 2023;16:1640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lee KH, Khan FN, Cosby L, Yang G, Winter JO. Polymer concentration maximizes encapsulation efficiency in electrohydrodynamic mixing nanoprecipitation. Front Nanotechnol. 2021;3:92.

    Article  Google Scholar 

  97. Van Krevelen DW, Te Nijenhuis K. Properties of polymers: their correlation with chemical structure; their numerical estimation and prediction from additive group contributions. Elsevier; 2009.

    Book  Google Scholar 

  98. Hansen CM. Hansen solubility parameters: a user’s handbook. CRC Press; 2007.

    Book  Google Scholar 

  99. Shi C, Sun Y, Wu H, Zhu C, Wei G, Li J, Chan T, Ouyang D, Mao S. Exploring the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading. Int J Pharm. 2016;512:282–91.

    Article  CAS  PubMed  Google Scholar 

  100. DeBoyace K, Wildfong PLD. The application of modeling and prediction to the formation and stability of amorphous solid dispersions. J Pharm Sci. 2018;107:57–74.

    Article  CAS  PubMed  Google Scholar 

  101. Potter CB, Davis MT, Albadarin AB, Walker GM. Investigation of the dependence of the flory-huggins interaction parameter on temperature and composition in a drug-polymer system. Mol Pharm. 2018;15:5327–35.

    Article  CAS  PubMed  Google Scholar 

  102. Meunier M, Goupil A, Lienard P. Predicting drug loading in PLA-PEG nanoparticles. Int J Pharm. 2017;526:157–66.

    Article  CAS  PubMed  Google Scholar 

  103. Luo Z, Jiang J. pH-sensitive drug loading/releasing in amphiphilic copolymer PAE–PEG: Integrating molecular dynamics and dissipative particle dynamics simulations. J Control Release. 2012;162:185–93.

    Article  CAS  PubMed  Google Scholar 

  104. Elbs H, Krausch G. Ellipsometric determination of Flory-Huggins interaction parameters in solution. Polymer. 2004;45:7935–42.

    Article  CAS  Google Scholar 

  105. Thakral S, Thakral NK. Prediction of drug-polymer miscibility through the use of solubility parameter based flory-huggins interaction parameter and the experimental validation: PEG as model polymer. J Pharm Sci. 2013;102:2254–63.

    Article  CAS  PubMed  Google Scholar 

  106. Yan J, Ye Z, Chen M, Liu Z, Xiao Y, Zhang Y, Zhou Y, Tan W, Lang M. Fine tuning micellar core-forming block of poly (ethylene glycol)-block-poly (ε-caprolactone) amphiphilic copolymers based on chemical modification for the solubilization and delivery of doxorubicin. Biomacromol. 2011;12:2562–72.

    Article  CAS  Google Scholar 

  107. Tian Y, Shi C, Sun Y, Zhu C, Sun CC, Mao S. Designing micellar nanocarriers with improved drug loading and stability based on solubility parameter. Mol Pharm. 2015;12:816–25.

    Article  CAS  PubMed  Google Scholar 

  108. Liu J, Xiao Y, Allen C. Polymer–drug compatibility: A guide to the development of delivery systems for the anticancer agent, ellipticine. J Pharm Sci. 2004;93:132–43.

    Article  CAS  PubMed  Google Scholar 

  109. Huynh L, Neale C, Pomes R, Allen C. Computational approaches to the rational design of nanoemulsions, polymeric micelles, and dendrimers for drug delivery. Nanomedicine. 2012;8:20–36.

    Article  CAS  PubMed  Google Scholar 

  110. Medarević D, Djuriš J, Barmpalexis P, Kachrimanis K, Ibrić S. Analytical and computational methods for the estimation of drug-polymer solubility and miscibility in solid dispersions development. Pharmaceutics. 2019;11:372.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Alskär LC, Porter CJH, Bergström CAS. Tools for early prediction of drug loading in lipid-based formulations. Mol Pharm. 2015;13:251–61.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Cern A, Barenholz Y, Tropsha A, Goldblum A. Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates for liposomal remote loading. J Control Release. 2014;173:125–31.

    Article  CAS  PubMed  Google Scholar 

  113. Zucker D, Marcus D, Barenholz Y, Goldblum A. Liposome drugs’ loading efficiency: A working model based on loading conditions and drug’s physicochemical properties. J Control Release. 2009;139:73–80.

    Article  CAS  PubMed  Google Scholar 

  114. Cern A, Golbraikh A, Sedykh A, Tropsha A, Barenholz Y, Goldblum A. Quantitative structure - property relationship modeling of remote liposome loading of drugs. J Control Release. 2012;160:147–57.

    Article  CAS  PubMed  Google Scholar 

  115. Mackenzie R, Booth J, Alexander C, Garnett MC, Laughton CA. Multiscale modeling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency. J Chem Theory Comput. 2015;11:2705–13.

    Article  CAS  PubMed  Google Scholar 

  116. Ansari M, Moradi S, Shahlaei M. A molecular dynamics simulation study on the mechanism of loading of gemcitabine and camptothecin in poly lactic-co-glycolic acid as a nano drug delivery system. J Mol Liq. 2018;269:110–8.

    Article  CAS  Google Scholar 

  117. Wang X-Y, Zhang L, Wei X-H, Wang Q. Molecular dynamics of paclitaxel encapsulated by salicylic acid-grafted chitosan oligosaccharide aggregates. Biomaterials. 2013;34:1843–51.

    Article  CAS  PubMed  Google Scholar 

  118. Durrant JD, McCammon JA. Molecular dynamics simulations and drug discovery. BMC Biol. 2011;9:1–9.

    Article  Google Scholar 

  119. Hu X, Zeng Z, Zhang J, Wu D, Li H, Geng F. Molecular dynamics simulation of the interaction of food proteins with small molecules. Food Chem. 2023;405: 134824.

    Article  CAS  PubMed  Google Scholar 

  120. Zhang A, Jung K, Li A, Liu J, Boyer C. Recent advances in stimuli-responsive polymer systems for remotely controlled drug release. Prog Polym Sci. 2019;99: 101164.

    Article  CAS  Google Scholar 

  121. Tibbitt MW, Dahlman JE, Langer R. Emerging frontiers in drug delivery. J Am Chem Soc. 2016;138:704–17.

    Article  CAS  PubMed  Google Scholar 

  122. Kang N, Perron M-È, Prud’Homme RE, Zhang Y, Gaucher G, Leroux J-C. Stereocomplex block copolymer micelles: Core− shell nanostructures with enhanced stability. Nano Lett. 2005;5:315–9.

    Article  CAS  PubMed  Google Scholar 

  123. Sun Q, Radosz M, Shen Y. Challenges in design of translational nanocarriers. J Control Release. 2012;164:156–69.

    Article  CAS  PubMed  Google Scholar 

  124. Zhu R, He Q, Li Z, Ren Y, Liao Y, Zhang Z, Dai Q, Wan C, Long S, Kong L, Fan W, Yu W. ROS-cleavable diselenide nanomedicine for NIR-controlled drug release and on-demand synergistic chemo-photodynamic therapy. Acta Biomater. 2022;153:442–52.

    Article  CAS  PubMed  Google Scholar 

  125. Ghosh B, Biswas S. Polymeric micelles in cancer therapy: State of the art. J Control Release. 2021;332:127–47.

    Article  CAS  PubMed  Google Scholar 

  126. Luo Z, Liu C, Quan P, Yang D, Zhao H, Wan X, Fang L. Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity. Acta Pharmaceutica Sinica B. 2020;10:928–45.

    Article  PubMed  Google Scholar 

  127. Wei C, Bai L, An X, Xu M, Liu W, Zhang W, Singh M, Shen K, Han Y, Sun L, Lin J, Zhao Q, Zhang Y, Yang Y, Yu M, Li Y, Sun N, Han Y, Xie L, Ou C, Sun B, Ding X, Xu C, An Z, Chen R, Ling H, Li W, Wang J, Huang W. Atomic-resolved hierarchical structure of elastic π-conjugated molecular crystal for flexible organic photonics. Chem. 2022;8:1427–41.

    Article  CAS  Google Scholar 

  128. Kuang H, Wu S, Meng F, Xie Z, Jing X, Huang Y. Core-crosslinked amphiphilic biodegradable copolymer based on the complementary multiple hydrogen bonds of nucleobases: synthesis, self-assembly and in vitro drug delivery. J Mater Chem. 2012;22:24832–40.

    Article  CAS  Google Scholar 

  129. Cheng CC, Lin IH, Chen JK, Liao ZS, Huang JJ, Lee DJ, Xin Z. Nucleobase-functionalized supramolecular micelles with tunable physical properties for efficient controlled drug release. Macromol Biosci. 2016;16:1415–21.

    Article  CAS  PubMed  Google Scholar 

  130. Abebe Alemayehu Y, Tewabe Gebeyehu B, Cheng C-C. Photosensitive supramolecular micelles with complementary hydrogen bonding motifs to improve the efficacy of cancer chemotherapy. Biomacromol. 2019;20:4535–45.

    Article  CAS  Google Scholar 

  131. Lee R-S, Peng K-Y, Wang S-W, Li Y-Z. Synthesis and characterization of amphiphilic poly(pseudo-amino acid) polymers containing a nucleobase. Polym J. 2014;46:710–21.

    Article  CAS  Google Scholar 

  132. Tian Y, Bromberg L, Lin S, Hatton TA, Tam KC. Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly (acrylic acid) block copolymers. J Control Release. 2007;121:137–45.

    Article  CAS  PubMed  Google Scholar 

  133. Li G, Song S, Guo L, Ma S. Self-assembly of thermo-and pH-responsive poly (acrylic acid)-b-poly (N-isopropylacrylamide) micelles for drug delivery. J Polym Sci, Part A: Polym Chem. 2008;46:5028–35.

    Article  CAS  Google Scholar 

  134. Pan Y-J, Chen Y-Y, Wang D-R, Wei C, Guo J, Lu D-R, Chu C-C, Wang C-C. Redox/pH dual stimuli-responsive biodegradable nanohydrogels with varying responses to dithiothreitol and glutathione for controlled drug release. Biomaterials. 2012;33:6570–9.

    Article  CAS  PubMed  Google Scholar 

  135. Johnson RP, Jeong YI, Choi E, Chung CW, Kang DH, Oh SO, Suh H, Kim I. Biocompatible poly(2-hydroxyethyl methacrylate)-b-poly(l-histidine) hybrid materials for pH-sensitive intracellular anticancer drug delivery. Adv Func Mater. 2011;22:1058–68.

    Article  Google Scholar 

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Funding

We acknowledge the financial support from the National Natural Science Foundation of China (Nos. 82373822 and 81973266), Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province (No. BK20230041), China Postdoctoral Science Foundation (No. 2023M733893), Jiansu Provincial Excellent Postdoctoral Program (No. 2023ZB838), Fundamental Research Funds for the Central Universities (No. 3012300081).

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  1. Enpeng Dong and Qingqing Huo contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, Department of Pharmaceutical Science, China Pharmaceutical University, Nanjing 210009, China

    Enpeng Dong, Qingqing Huo, Jie Zhang, Hanghang Han, Ting Cai & Dongfei Liu

  2. NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China

    Enpeng Dong, Qingqing Huo, Jie Zhang, Hanghang Han & Dongfei Liu

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  1. Enpeng Dong
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Contributions

All authors listed have contributed significantly to the article. Enpeng Dong, Qingqing Huo, Jie Zhang, Hanghang Han were involved in editing and initial draft creation. Enpeng Dong, Qingqing Huo, Jie Zhang, Hanghang Han, Ting Cai, and Dongfei Liu participated in writing, editing, and critically revising the intellectual content. Qingqing Huo, Ting Cai, and Dongfei Liu were responsible for conceptualization and supervision. All authors have read and approved the final manuscript.

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Dong, E., Huo, Q., Zhang, J. et al. Advancements in nanoscale delivery systems: optimizing intermolecular interactions for superior drug encapsulation and precision release. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01579-w

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