Micelle-Loaded Oral Dissolvable Strips: A Novel Strategy to Enhance Bioavailability and Pharmacokinetics of Therapeutics

Authors

  • Katharine H. Cole CTT Pharmaceuticals, Tampa, Florida
  • Pankaj Modi CTT Pharmaceuticals, Tampa, Florida

Abstract

Background: This review examines the technology and therapeutic potential of oral dissolvable strips (ODS) loaded with micellized active pharmaceutical ingredients (APIs) for improved systemic drug delivery. Oral dissolvable strips (ODS) have emerged as a convenient and patient friendly route for drug delivery; however, many APIs exhibit poor aqueous solubility and stability, limiting their therapeutic efficiency. Micellar nanocarriers embedded in ODS can overcome these limitations by improving the solubility, stability, pharmacokinetics, and bioavailability.

Objective: This review evaluates the integration of micelle technology with ODS platforms to improve systemic absorption and therapeutic performance of APIs, focusing on formulation advances, pharmacokinetic improvements, and translational challenges.

Methods: Peer-reviewed research articles, patents, and reviews related to micellized APIs and oral film drug delivery systems were analyzed to identify formulation strategies, physicochemical optimization approaches, and clinical implications for diverse APIs.

Results: Micelle-embedded oral films enable efficient delivery of hydrophobic drugs, produce faster absorption and achieve higher plasma concentrations than conventional oral routes. By improving patient compliance, minimizing toxicity, and protecting APIs from hepatic and gastrointestinal degradation, micelle/ODS systems significantly enhance bioavailability. Challenges exist with formulation variables such as micelle composition and film thickness which affect release kinetics, and optimization and stabilization of micellized APIs.

Conclusion: Integrating micellar nanotechnology with oral dissolvable strips represents a promising next-generation platform for effective, non-invasive, and patient-compliant oral drug delivery. This technology holds great potential for delivering prescription drugs, supplements, chemotherapeutics, and biologics. Future investigations should prioritize optimizing formulation strategies and scalable manufacturing processes, clarifying regulatory pathways, and designing clinical trials.

Keywords: micelle, oral dissolvable strip, bioavailability, pharmacokinetics, drug delivery

Keywords:

micelle, oral dissolvable strip, bioavailability, pharmacokinetics, drug delivery

DOI

https://doi.org/10.22270/jddt.v15i12.7441

Author Biographies

Katharine H. Cole, CTT Pharmaceuticals, Tampa, Florida

CTT Pharmaceuticals, Tampa, Florida

Pankaj Modi, CTT Pharmaceuticals, Tampa, Florida

CTT Pharmaceuticals, Tampa, Florida

References

1. Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in oral drug delivery. Front Pharmacol. 2021;12:618411. https://doi.org/10.3389/fphar.2021.618411 PMid:33679401 PMCid:PMC7933596

2. Loke YH, Tan ML, Khor SY. A comprehensive review of challenges in oral drug delivery systems and recent advancements in innovative design strategies. Curr Pharm Des. 2025;31(5):360-376. https://doi.org/10.2174/0113816128338560240923073357 PMid:39390835

3. Saxena A, Singh T. Oral dissolving films: a comprehensive review on recent perspectives and current approach to effective drug delivery. J Drug Deliv Ther. 2022;12(2):139-147. https://doi.org/10.22270/jddt.v12i2.5244

4. Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci. 1998;1(1):15-30. https://doi.org/10.1023/A:1011927521627 PMid:9706047

5. Salawi A. An insight into preparatory methods and characterization of orodispersible films-a review. Pharmaceuticals. 2022;15(7):844. https://doi.org/10.3390/ph15070844 PMid:35890143 PMCid:PMC9323338

6. Bala R, Pawar P, Khanna S, Arora S. A new approach to oral drug delivery system. J Adv Pharm Technol Res. 2013;4(1):5-12. doi:10.4103/2231-4040.107494. https://doi.org/10.4103/2231-4040.107494 PMid:23662276 PMCid:PMC3645360

7. Özakar RS, Çelik B, Yenilmez E, Yazan Y. Current overview of oral thin films. Pharmaceutics. 2021;13(11):1950. https://doi.org/10.3390/pharmaceutics13111950 PMid:34834365 PMCid:PMC8618763

8. Shipp L, Liu F, Kerai-Varsani L, Okwuosa TC. Buccal films: a review of therapeutic opportunities, formulations & relevant evaluation approaches. J Control Release. 2022;352:1071-1092. https://doi.org/10.1016/j.jconrel.2022.10.058 PMid:36351519

9. Gupta MS, Ahirrao SP, Mahajan NS. Orodispersible films: conception to quality by design. Int J Pharm. 2021;607:120924. https://doi.org/10.1016/j.ijpharm.2021.120924 PMid:34324989 PMCid:PMC8579814

10. Ghourichay MP, Esfandiari N, Ghasemi S, et al. Formulation and quality control of orally disintegrating films. Int J Pharm Sci Res. 2021;12(3):1328-1339. https://doi.org/10.1155/2021/6618934 PMid:34977245 PMCid:PMC8719989

11. Kay J, Smith L, Wimmer P, et al. Simultaneous quantitation of water and residual solvents in pharmaceutical films. J Pharm Biomed Anal. 2021;197:113953. https://doi.org/10.1016/j.jpba.2021.113953 PMid:33618130

12. Ferlak J, Szymanska E, Sosnowska K, et al. Orodispersible films-current state of the art, limitations and future perspectives. Pharmaceutics. 2023;15(2):361. https://doi.org/10.3390/pharmaceutics15020361 PMid:36839683 PMCid:PMC9965071

13. Lombardo D, Kiselev MA, Caccamo MT. Amphiphiles self-assembly: basic concepts and future perspectives. Adv Colloid Interface Sci. 2015;222:124-137. https://doi.org/10.1155/2015/151683

14. Haladjova E, Rangelov S. Application of polymeric micelles for drug and gene delivery. Pharmaceutics. 2024;16(5):646. https://doi.org/10.3390/pharmaceutics16050646 PMid:38794308 PMCid:PMC11125079

15. Kotta S, Aldawsari HM, Badr-Eldin SM, Nair AB. Progress in polymeric micelles for drug delivery applications. Pharmaceutics. 2022;14(8):1636. https://doi.org/10.3390/pharmaceutics14081636 PMid:36015262 PMCid:PMC9412594

16. Hwang D, Kim J, Park E, Lee S, Yoon S. Polymeric micelles for the delivery of poorly soluble drugs. Pharmaceutics. 2020;12(6):512.

17. Weng W, Wang Q, Wei C, et al. Mixed micelles for enhanced oral bioavailability and hypolipidemic effect of liquiritin: in vitro and in vivo evaluation. Drug Dev Ind Pharm. 2021;47(8):1258-1267. https://doi.org/10.1080/03639045.2021.1879839 PMid:33494627

18. Lu H, Zhang S, Wang J and Chen Q. A Review on Polymer and Lipid-Based Nanocarriers and Its Application to Nano-Pharmaceutical and Food-Based Systems. Front. Nutr. 2021; 8:783831. https://doi.org/10.3389/fnut.2021.783831 PMid:34926557 PMCid:PMC8671830

19. Hoffmann EM, Breitenbach A, Breitkreutz J. Advances in orodispersible films for drug delivery. Eur J Pharm Biopharm. 2011;77(2):197-208. https://doi.org/10.1517/17425247.2011.553217 PMid:21284577

20. Silva BMA, Borges AF, Silva C, Coelho JFJ, Simões S. Mucoadhesive oral films: the potential for unmet needs. Int J Pharm. 2015;494(1):537-551. https://doi.org/10.1016/j.ijpharm.2015.08.038 PMid:26315122

21. Jaiswal H, Shikhande S, More DM, Kadam VJ. Recent trends in formulation of oral dissolving films: A review. Int J PharmTech Res. 2014;6(2):1054-1066.

22. Karki S, Kim H, Na SJ, Shin D, Jo K, Lee J. Thin films as an emerging platform for drug delivery. Asian J Pharm Sci. 2016;11(5):559-574. https://doi.org/10.1016/j.ajps.2016.05.004

23. Ma Y, Zhao L, Liu H, et al. Development and pharmacokinetics of an everolimus-loaded sublingual orodispersible film. Eur J Pharm Biopharm. 2020;149:19-27.

24. Aldawsari HM, Badr-Eldin SM. Formulation and evaluation of dapoxetine hydrochloride oral dissolving films for improved pharmacokinetics and patient compliance. Pharmaceutics. 2020;12(3):210.

25. Irfan M, Rabel S, Bukhtar Q, et al. Orally disintegrating films: a modern expansion in drug delivery. Saudi Pharm J. 2016;24(5):537-546. https://doi.org/10.1016/j.jsps.2015.02.024 PMid:27752225 PMCid:PMC5059831

26. Liu C, Wang Y, Luo W, et al. Fast-dissolving oral films containing luteolin nanocrystals: pharmacokinetics and bioavailability. Drug Dev Ind Pharm. 2017;43(11):1843-1851.

27. Radicioni M, Cattaneo C, Ronchi L, et al. Comparative bioavailability of vitamin D₃ orally disintegrating film versus solution. Nutrients. 2022;14(10):2005.

28. Liu W, Wang Y, Lou Y, Zhang J, Zhang L, Guo R, Zhang Q. Design and evaluation of orally dissolving films: a novel strategy for stable delivery of moisture-sensitive drugs. Drug Dev Ind Pharm. 2017;43(5):828-838. doi:10.1080/03639045.2016.1267855.

29. Pacheco MS, Barbieri D, da Silva CF, de Moraes MA. A review on orally disintegrating films (ODFs) made from natural polymers such as pullulan, maltodextrin, starch, and others. Int J Biol Macromol. 2021;178:504-513. https://doi.org/10.1016/j.ijbiomac.2021.02.180 PMid:33647337

30. He Y, Cheng X, Wang Q, Liu Y, et al. Stabilization of vitamin B12 in oral dissolving films using xanthan and pullulan. Drug Dev Ind Pharm. 2021;47(5):775-784. doi:10.1080/03639045.2021.1901589.

31. Qin Z-Y, Jia X-W, Liu Q, Kong B-H, Wang H. Fast dissolving oral films for drug delivery prepared from chitosan/pullulan electrospinning nanofibers. Int J Biol Macromol. 2019;137:224-231. https://doi.org/10.1016/j.ijbiomac.2019.06.224 PMid:31260763

32. Chen L-H, Doyle PS. Thermogelling hydroxypropyl methylcellulose nanoemulsions as templates to formulate poorly water-soluble drugs into oral thin films containing drug nanoparticles. Chem Mater. 2022;34(11):5194-5205. https://doi.org/10.1021/acs.chemmater.2c00801

33. Silvestre SM, Pereira AR, Sousa JM, et al. Orally dissolving films as patient-friendly dosage forms: formulation strategies for incorporating vitamins and supplements. Pharmaceutics. 2023;15(4):1082. https://doi.org/10.3390/pharmaceutics15041082 PMid:37111568 PMCid:PMC10145306

34. Takashima Y, Nishikawa M, Ueda H, et al. Development of oral dissolving films for delivery of prescription drugs: physicochemical properties and patient acceptability. Drug Dev Ind Pharm. 2022;48(9):197-205. doi:10.1080/03639045.2022.2034025

35. Batista P, Silva AC, Fernandes C. Overview of oral thin films for nutrient and supplement delivery: formulation and regulatory trends. J Drug Deliv Sci Technol. 2023;80:104110. https://doi.org/10.1016/j.jddst.2022.104110

36. Cupone I, Brunetti L, Musazzi UM, Selmin F, Minghetti P. Orodispersible polymeric films containing nutraceuticals: manufacturing approaches and characterization. Int J Pharm. 2023;636:122756. doi:10.1016/j.ijpharm.2023.122756.

37. Mazumder S, Pavurala N, Manda P, Xu X, Cruz CN, Krishnaiah YSR. Quality by design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films. Int J Pharm. 2017;527(1-2):151-160. https://doi.org/10.1016/j.ijpharm.2017.05.048 PMid:28549972

38. Shojaee Kang Sofla M, Mortazavi S, Seyfi J. Preparation and characterization of polyvinyl alcohol/chitosan blends plasticized and compatibilized by glycerol/polyethylene glycol. Carbohydr Polym. 2020;232:115784. https://doi.org/10.1016/j.carbpol.2019.115784 PMid:31952592

39. Abou-Taleb H, El-Zahaby SA, Abdelrahim MEA. Sweeteners as taste-masking agents in orodispersible vardenafil films. Pharmaceutics. 2022;14(6):1229. https://doi.org/10.3390/pharmaceutics14030517 PMid:35335893 PMCid:PMC8951028

40. Shruthi BK, Chandrakala V, Srinivasan S. Role of Super Disintegrants in Rapid Dissolving Oral Films. Int J Pharm Sci Rev Res. 2022;75(2):110-116. https://doi.org/10.47583/ijpsrr.2022.v75i02.018

41. Desai PM, Liew CV, Heng PWS. Review of disintegrants and the disintegration phenomena. J Pharm Sci. 2016;105(9):2545-2555. https://doi.org/10.1016/j.xphs.2015.12.019 PMid:27506604

42. Panraksa P, Tipduangta P, Jantanasakulwong K, Jantrawut P. Formulation of orally disintegrating films as an amorphous solid solution of a poorly water-soluble drug. Membranes. 2020;10(12):376. https://doi.org/10.3390/membranes10120376 PMid:33261025 PMCid:PMC7759778

43. Alghaith AF, Alshahrani SM, Almehmadi MM, et al. Plasticizers in oral thin films: influence on mechanical strength and dissolution rate. Int J Pharm Sci Rev Res. 2022;72(1):45-54.

44. Baskaran R, Madheswaran T, Sundaramoorthy P, Kim HM, Yoo BK. Novel chitosan-based polymeric films for oral drug delivery. Carbohydr Polym. 2017;157:1800-1808.

45. Cheng X, Wang Q, Liu Y, et al. Stabilization of vitamin B12 in oral dissolving films using xanthan and pullulan. Drug Dev Ind Pharm. 2021;47(5):775-784.

46. Lambros M, Tran TH, Fei Q, Nicolaou M. Citric Acid: A Multifunctional Pharmaceutical Excipient. Pharmaceutics. 2022;14(5):972. https://doi.org/10.3390/pharmaceutics14050972 PMid:35631557 PMCid:PMC9148065

47. Wexler C, Patel A, Bhatt J, Narang AS. Patient acceptability and pharmacological implications of oral thin films: a review. J Drug Deliv Sci Technol. 2023;81:104327. https://doi.org/10.1016/j.jddst.2023.104327

48. Heinemann RJB, Carvalho RA, Favaro-Trindade CS. Orally disintegrating film (ODF) for delivery of probiotics in the oral cavity - development of a novel product for oral health. Innov Food Sci Emerg Technol. 2013;19:227-232. https://doi.org/10.1016/j.ifset.2013.04.009

49. Yu X, Wang L, Zhang H, Li J, Chen Y, Zhao Y. Curcumin oral thin films for improved solubility and patient compliance. J Pharm Innov. 2022;17(4):995-1007. doi:10.1007/s12247-021-09667-2.

50. Bartlett AL, Zhang G, Wallace G, Gordon CM, Freishtat RJ, Reynolds JC, et al. Optimized vitamin D repletion with oral thin-film cholecalciferol. Pediatr Transplant. 2023;27(4):e14936. doi:10.1111/petr.14936.

51. Trimaille T, Morin L, Dubois C, Brossard P-M, Couvreur P. Micellar nanocarriers: design, drug-loading, and stimuli-responsive release. Adv Drug Deliv Rev. 2023;192:114620. https://doi.org/10.1016/j.addr.2022.114620 PMid:36379406

52. Kato Y, Nishiyama N, Bae Y, Fukushima S, Yasuoka A, Koyama H, et al. Novel block copolymer micelles for drug delivery: design and behavior. J Control Release. 2007;124(1-2):43-50. https://doi.org/10.1016/j.jconrel.2007.08.006 PMid:17826863 PMCid:PMC2196406

53. Ghezzi M, Pescina S, Padula C, et al. Polymeric micelles in drug delivery: an insight into techniques for their characterization and assessment in biorelevant conditions. J Control Release. 2021;332:312-336. https://doi.org/10.1016/j.jconrel.2021.02.031 PMid:33652113

54. Zhou Z, Li Y, Wang S, et al. Smart polymeric micelles for targeted and controlled drug delivery. Eur J Pharm Biopharm. 2018;128:112-125.

55. Nakayama M, Akimoto J, Okano T. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting. J Drug Target. 2014;22(7):584-599. https://doi.org/10.3109/1061186X.2014.936872 PMid:25012066

56. Jhaveri AM, Torchilin VP. Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol. 2014;5:77. https://doi.org/10.3389/fphar.2014.00077 PMid:24795633 PMCid:PMC4007015

57. Prencipe G, Sardo C, De Tursi M, Leone C, Favia P, Centrone M, et al. Polymeric micelles decorated with targeting bioactive moieties as drug delivery systems in precision medicine. Molecules. 2021;26(13):4049. https://doi.org/10.3390/molecules26134049 PMid:34279392 PMCid:PMC8271712

58. Wang Y, Lin M, Fan T, Zhou M, Yin R, Wang X. Advances of stimuli-responsive amphiphilic copolymer micelles in tumor therapy. Int J Nanomedicine. 2025;20:1-24. https://doi.org/10.2147/IJN.S495387 PMid:39776491 PMCid:PMC11700880

59. Qiu N, Wang H, Li Y, Zhou Z, Zhao Y, Pan F, et al. A review of stimuli-responsive polymeric micelles for tumour therapy. J Drug Target. 2021;29(9):971-986. doi:10.1080/1061186X.2021.1934869.

60. Li Y, Xiao K, Zhu W, Deng W, Lam KS. Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers. Adv Drug Deliv Rev. 2014;66:58-73. https://doi.org/10.1016/j.addr.2013.09.008 PMid:24060922 PMCid:PMC3947689

61. Rao NV, Ko H, Lee J, Park JH. Recent progress and advances in stimuli-responsive polymers for cancer therapy. Front Bioeng Biotechnol. 2018;6:110. https://doi.org/10.3389/fbioe.2018.00110 PMid:30159310 PMCid:PMC6104418

62. Cao Z, Zhao M, Wu W, et al. Recent progress in stimuli-responsive polymeric micelles for drug delivery. Prog Polym Sci. 2024;146:101749. doi:10.1016/j.progpolymsci.2024.101749

63. Younis MA, Bnyan R, Railkar A, et al. Clinical translation of nanomedicines: challenges, opportunities, and strategies. Adv Drug Deliv Rev. 2022;181:114078. https://doi.org/10.1016/j.addr.2021.114078 PMid:34896131

64. Ahmed T, Liu FCF, Wu XY. An update on strategies for optimizing polymer-lipid hybrid nanoparticle-mediated drug delivery: exploiting transformability and bioactivity of PLN and harnessing intracellular lipid transport mechanism. Expert Opin Drug Deliv. 2024;21(2):245-278. https://doi.org/10.1080/17425247.2024.2318459 PMid:38344771

65. Hassan AAA, Ramadan E, Kristó K, Regdon Jr G, Sovány T. Lipid-polymer hybrid nanoparticles as a smart drug delivery platform: synthesis, characterization and oral delivery applications. Pharmaceutics. 2025;16(5):646. https://doi.org/10.3390/pharmaceutics16050646 PMid:38794308 PMCid:PMC11125079

66. Gajbhiye V, Khopade AJ, Jain NK. Polymeric-lipid hybrid micelles: an emerging platform for drug and gene delivery. Pharmaceutics. 2023;15(4):1102. https://doi.org/10.3390/pharmaceutics15041102 PMid:37111588 PMCid:PMC10142540

67. Perumal S, Atchudan R, Lee W. A review of polymeric micelles and their applications. Polymers. 2022;14(12):2510. https://doi.org/10.3390/polym14122510 PMid:35746086 PMCid:PMC9230755

68. Lu Y, Yue Z, Xie J, Wang W, Zhu H, Zhang E, et al. Micelles with ultralow critical micelle concentration as carriers for drug delivery. Nat Biomed Eng. 2018;2(5):318-325. https://doi.org/10.1038/s41551-018-0234-x PMid:30936455 PMCid:PMC6553490

69. Zeng Y, Li S, Chen X, et al. Soluplus® micelles for improving the oral bioavailability of scopoletin. Acta Pharm Sin B. 2017;7(2):162-169.

70. Guembe-Michel N, Nguewa P, González-Gaitano G. Soluplus®-based pharmaceutical formulations: recent advances in drug delivery and biomedical applications. Int J Mol Sci. 2025;26(4):1499. https://doi.org/10.3390/ijms26041499 PMid:40003966 PMCid:PMC11855892

71. Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems. J Control Release. 2001;73(2-3):137-172. https://doi.org/10.1016/S0168-3659(01)00299-1 PMid:11516494

72. Cabral H, Kataoka K. Progress of drug-loaded polymeric micelles into clinical studies. J Control Release. 2014;190:465-476. https://doi.org/10.1016/j.jconrel.2014.06.042 PMid:24993430

73. Cagel M, Tesán FC, Bernabeu E, Salgueiro MJ, Zubillaga MB, Moretton MA, Chiappetta DA. Polymeric mixed micelles as nanomedicines: achievements and perspectives. Eur J Pharm Biopharm. 2017;113:211-228. https://doi.org/10.1016/j.ejpb.2016.12.019 PMid:28087380

74. Chougale R, Patil K, Disouza J, Hajare A, Jadhav N, Kumbhar P, et al. Development of docetaxel-loaded (Soluplus®-PF108) mixed micelles vacuum foam-dried product for improved stability and melanoma treatment by QbD approach. Futur J Pharm Sci. 2024;10:54. https://doi.org/10.1186/s43094-024-00619-z

75. Feng S, Zhang Z, Almotairy A, Repka MA. Development and evaluation of polymeric mixed micelles prepared using hot-melt extrusion for extended delivery of poorly water-soluble drugs. J Pharm Sci. 2023;112(11):2869-2878. https://doi.org/10.1016/j.xphs.2023.06.007 PMid:37327994

76. Gerardos AM, Balafouti A, Pispas S. Mixed copolymer micelles for nanomedicine. Materials (Basel). 2023;15(2):2015. https://doi.org/10.3390/nanomanufacturing3020015

77. Negut I, Bita B. Polymeric micellar systems - a special emphasis on "smart" drug delivery. Pharmaceutics. 2023;15(3):976. https://doi.org/10.3390/pharmaceutics15030976 PMid:36986837 PMCid:PMC10056703

78. Duong VA, Tran MH, Phan TTK, Nguyen TTH. Inhibition of P-glycoprotein efflux and enhancement of drug absorption in oral nanocarriers: current status and future directions. Pharmaceutics. 2021;13(8):1227. https://doi.org/10.3390/pharmaceutics13081227 PMid:34452188 PMCid:PMC8398642

79. Sun S, Zheng T, Wu Y, Zhang Y, Zhou Q. Mixed polymer-lipid micelles of PEG-PLA/TPGS for enhanced oral delivery of galactosamine-modified drug: effects on absorption and epithelial transport. Int J Pharm. 2021;603:120699. https://doi.org/10.1016/j.ijpharm.2021.120699 PMid:33992713

80. Piazzini V, Landucci E, Urru M, Chiarugi A, Pellegrini-Giampietro DE, Bilia AR, Bergonzi MC. Enhanced dissolution, permeation and oral bioavailability of aripiprazole mixed micelles: in vitro and in vivo evaluation. Int J Pharm. 2020;583:119361. https://doi.org/10.1016/j.ijpharm.2020.119361 PMid:32334067

81. Zheng H, Bai Y, Tang G, et al. Stimuli-responsive polymeric micelles for controlled drug delivery in oncology. Adv Drug Deliv Rev. 2024;205:115-131.

82. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev. 2001;47(1):113-131. https://doi.org/10.1016/S0169-409X(00)00124-1 PMid:11251249

83. Ahmad Z, Shah A, Siddiq M, Kraatz HB. Polymeric micelles as drug delivery vehicles. RSC Adv. 2014;4:17028-17038. https://doi.org/10.1039/C3RA47370H

84. Zhou Y, Li Y, Yuan J, Xu C, Li J, Kang C, et al. Mixed polymeric micelles for drug delivery: preparation, characterization and applications. J Control Release. 2018;272:74-87. https://doi.org/10.1016/j.jconrel.2018.01.005 PMid:29331580

85. Trimaille T. Copolymer micelles: a focus on recent advances for protein/peptide delivery. Pharmaceutics. 2023;15(10):2481. https://doi.org/10.3390/pharmaceutics15102481 PMid:37896241 PMCid:PMC10609739

86. Mukherjee A, Waters AK, Kalyan P, Achrol AS, Kesari S, Yenugonda VM. Lipid-polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives. Int J Nanomedicine. 2019;14:1937-1952. https://doi.org/10.2147/IJN.S198353 PMid:30936695 PMCid:PMC6430183

87. Neguț I, Bita AI. Polymeric micelles: tumor targeting and delivery. Pharmaceutics. 2023;15(4):1129. https://doi.org/10.3390/pharmaceutics15030976 PMid:36986837 PMCid:PMC10056703

88. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release. 2002;82(2-3):189-212. https://doi.org/10.1016/S0168-3659(02)00009-3 PMid:12175737

89. Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC. Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release. 2005;109(1-3):169-188. https://doi.org/10.1016/j.jconrel.2005.09.034 PMid:16289422

90. Porter CJH, Pouton CW, Cuine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev. 2008;60(6):673-691. https://doi.org/10.1016/j.addr.2007.10.014 PMid:18155801

91. Zhao Y, Wang C, Chow AH-L, Ren K, Gong T, Zhang Z, et al. Stable phosphatidylcholine-bile salt mixed micelles to enhance intestinal absorption of paclitaxel in rats. Int J Pharm. 2014;473(1-2):474-484. https://doi.org/10.1016/j.ijpharm.2014.07.027 PMid:25066077

92. Kotake-Nara E, Komba S, Hase M. Uptake of vitamins D2, D3, D4, D5, D6, and D7 solubilized in mixed micelles by human intestinal cells, Caco-2, and an enhancing effect of lysophosphatidylcholine on the cellular uptake. Nutrients. 2021;13(5):1555. https://doi.org/10.3390/nu13051555 PMid:34063058 PMCid:PMC8147969

93. Saxena V, Delwar Hussain M. Polymeric mixed micelles for delivery of curcumin to multidrug resistant ovarian cancer. J Biomed Nanotechnol. 2013;9(7):1146-1153. https://doi.org/10.1166/jbn.2013.1632 PMid:23909128

94. Islam N, Irfan M, Khan SU, Syed HK, Iqbal MS, Khan IU, Mahdy A, Raafat M, Hossain MA. Poloxamer-188 and d-α-tocopheryl polyethylene glycol succinate (TPGS-1000) mixed micelles integrated into orodispersible sublingual films to improve oral bioavailability of ebastine. Pharmaceutics. 2021;13(1):54. https://doi.org/10.3390/pharmaceutics13010054 PMid:33406587 PMCid:PMC7823785

95. Wei Z, Zhu D, Ma Y, Wen Y, Wang Z, Li L. Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vivo evaluation. Int J Pharm. 2009;373(1-2):189-196. https://doi.org/10.1016/j.ijpharm.2009.03.036 PMid:19428198

96. Bae Y, Nishiyama N, Fukushima S, Koyama H, Matsumura Y, Kataoka K. Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjug Chem. 2005;16(1):122-130. https://doi.org/10.1021/bc0498166 PMid:15656583

97. Han Y, Li J, Zan M, Luo S, Ge Z, Liu S. Redox-responsive core cross-linked micelles based on cypate- and cisplatin-prodrug-conjugated block copolymers for synergistic photothermal-chemotherapy of cancer. Polym Chem. 2014;5(12):3707-3719. https://doi.org/10.1039/C4PY00064A

98. Nasongkla N, Shuai X, Ai H, Weinberg BD, Pink J, Boothman DA, et al. cRGD-functionalized polymer micelles for targeted doxorubicin delivery. Angew Chem Int Ed. 2004;43(46):6323-6327. https://doi.org/10.1002/anie.200460800 PMid:15558662

99. Peng J, Qi T, Liao J, Chu X, Wu Q, Guo X, et al. Herceptin-conjugated paclitaxel-loaded PCL-PEG worm-like micelles for HER2-positive breast cancer therapy. J Control Release. 2019;311-312:136-149. https://doi.org/10.1016/j.jconrel.2019.08.001 PMid:31381942

100. Cai Y, et al. The in vivo fate of polymeric micelles. J Control Release. 2022;349:640-658. https://doi.org/10.1016/j.jconrel.2022.03.032 PMid:35331783 PMCid:PMC8935967

101. Zhang W, Shi Y, Chen Y, Yu S, Hao J, Luo J. Enhanced antitumor efficacy by paclitaxel-loaded mixed micelles composed of Pluronic P123 and D-α-tocopheryl polyethylene glycol succinate 1000. Mol Pharm. 2019;16(3):1072-1084.

102. Tyrrell ZL, Shen Y, Radosz M. Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers. Prog Polym Sci. 2010;35(9):1128-1143. https://doi.org/10.1016/j.progpolymsci.2010.04.002

103. Zhang L, Li X, Zhao H, et al. Antisolvent precipitation for improving solubility and dissolution of poorly water-soluble drugs: strategies and recent advances. Eur J Pharm Sci. 2022;170:106122. https://doi.org/10.1016/j.ejps.2022.106122 PMid:35007712

104. Jaiswal H, Shikhande S, More DM, Kadam VJ. Recent trends in formulation of oral dissolving films: A review. Int J PharmTech Res. 2014;6(2):1054-1066.

105. Chou WH, Galaz A, Jara MO, Gamboa A, Morales JO. Drug-loaded lipid-core micelles in mucoadhesive films as a novel dosage form for buccal administration of poorly water-soluble and biological drugs. Pharmaceutics. 2020;12(12):1168. https://doi.org/10.3390/pharmaceutics12121168 PMid:33266132 PMCid:PMC7761273

106. Prajapati BG, Patel MM, et al. Mixed micelle sublingual films of curcumin for enhanced bioavailability. Drug Dev Ind Pharm. 2023;49(1):1-10.

107. Chen K, Sun Y. Development and optimization of oral dissolution films for enhanced delivery of ebastine-loaded solid lipid nanoparticles. Int J Nanomedicine. 2025;20:6963-6981. https://doi.org/10.2147/IJN.S521504 PMid:40462833 PMCid:PMC12132053

108. Patel C, Pujari R, Rede P, Prajapati B, Dharamsi A. The electro-spun sublingual film containing curcumin micelles. J Nat Remedies. 2023;23(1):206-213.

109. Elshafeey AH, El-Dahmy RM. Formulation and development of oral fast-dissolving films loaded with nanosuspension to augment paroxetine bioavailability: in vitro characterization, ex vivo permeation, and pharmacokinetic evaluation in healthy human volunteers. Pharmaceutics. 2021;13(11):1869. https://doi.org/10.3390/pharmaceutics13111869 PMid:34834284 PMCid:PMC8620498

110. Nagar P, Chauhan I, Yasir M. Insights into polymers: film formers in mouth dissolving films. Drug Invent Today. 2011;3(12):280-289.

111. Hussain Z, Pandey M, Chauhan M, et al. Optimization of solvent casting parameters for polymeric micelle-loaded oral films. J Drug Deliv Sci Technol. 2023;79:104012.

112. Ferlak J, Krupa A, Stompor-Gorący M. Orodispersible films-current state of the art, limitations and future directions. Pharmaceutics. 2023;15(2):361. https://doi.org/10.3390/pharmaceutics15020361 PMid:36839683 PMCid:PMC9965071

113. Steiner D, Pfaffenbach J, Brandl M. Orodispersible films: a delivery platform for solid lipid nanoparticles. Pharmaceutics. 2021;13(12):2162. https://doi.org/10.3390/pharmaceutics13122162 PMid:34959444 PMCid:PMC8709056

114. Tzanova MM, Kassarova MI, Ginevskaya VT, Tzankova V. Solid lipid nanoparticle-loaded mucoadhesive buccal films. Int J Pharm. 2021;599:120420. https://doi.org/10.1016/j.ijpharm.2021.120420 PMid:33647404

115. Kumar R, et al. Mucoadhesive carriers for oral drug delivery. Adv Drug Deliv Rev. 2022;187:114360. https://doi.org/10.1016/j.addr.2022.114360 PMid:35636568

116. Sandri G, et al. The role of chitosan as a mucoadhesive agent in mucosal drug delivery. J Drug Deliv Sci Technol. 2012;22(5):275-284. https://doi.org/10.1016/S1773-2247(12)50046-8

117. Alaei S, et al. Mucoadhesion and mechanical assessment of oral films. J Pharm Pharm Sci. 2021;24:1-20. doi:10.18433/jpps31815.

118. Jacob S, Nair AB, Shah J. An updated overview of the emerging role of patch and film-based buccal delivery systems. Pharmaceutics. 2021;13(8):1206. https://doi.org/10.3390/pharmaceutics13081206 PMid:34452167 PMCid:PMC8399227

119. Mahmood A, Lanthaler M, Laffleur F, Bernkop-Schnürch A. Thiolated polymeric micelles: Highly mucoadhesive drug carrier systems. Eur J Pharm Biopharm. 2017;115:102-108. https://doi.org/10.1016/j.ejpb.2017.02.014 PMid:28232106

120. Dyawanapelly S, Dandekar P, Jain R, Tiwari D, Sharma S, Belgamwar V, et al. Improved oral bioavailability of curcumin using thiolated chitosan nanoparticles: role of mucoadhesion and efflux transport inhibition. Drug Deliv Transl Res. 2016;6(4):420-431. https://doi.org/10.1007/s13346-016-0295-x PMid:27106502

121. Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. Eur J Pharm Biopharm. 2010;74(2):251-256. https://doi.org/10.1016/j.ejpb.2009.08.007 PMid:19723580

122. Torchilin VP. Micellar nanocarriers: pharmaceutical perspectives. Pharm Res. 2007;24(1):1-16. https://doi.org/10.1007/s11095-006-9132-0 PMid:17109211

123. Narang AS, Delmarre D. Oral bioavailability and stability of nanosized drug carriers. Drug Discov Today. 2021;26(3):758-769.

124. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent SMANCS. Cancer Res. 1986;46(12):6387-6392.

125. Wu J. The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application. J Pers Med. 2021;11(8):771. https://doi.org/10.3390/jpm11080771 PMid:34442415 PMCid:PMC8402171

126. 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):278-287. https://doi.org/10.1016/j.ejps.2006.04.016 PMid:16815001

127. Preis M, Woertz C, Kleinebudde P, Breitkreutz J. Oromucosal film preparations: classification and characterization methods. Expert Opin Drug Deliv. 2013;10(9):1303-1317. https://doi.org/10.1517/17425247.2013.804058 PMid:23768198

128. Gil MC, Park SJ, Lee BS, Park C, Lee BJ. Dual thermal stabilizing effects of xanthan gums via glycosylation and hydrogen bonding and in vivo human bioavailability of desmopressin in orodispersible film. Int J Pharm. 2023;637:122879. https://doi.org/10.1016/j.ijpharm.2023.122879 PMid:36958609

129. De'Nobili MD, Pérez AA, Andina N, Descalzo AM. Stability of L-(+)-ascorbic acid in alginate edible films: effect of film composition and storage conditions. Food Hydrocoll. 2016;58:82-90. https://doi.org/10.1016/j.foodhyd.2016.02.030

130. Emami F, Vatanara A. Recent progress in drying technologies for improving the stability of biopharmaceuticals. AAPS PharmSciTech. 2023;24(4):162. doi:10.1208/s12249-023-02514-0.

131. Myers GL, Peura RA, Stepensky D, inventors; MonoSol Rx LLC, assignee. Uniform films for rapid-dissolve dosage forms. US patent 9,855,221 B2. 2018 Jan 2.

132. Myers GL, Peura RA, Stepensky D, inventors; MonoSol Rx LLC, assignee. Uniform films for rapid-dissolve dosage forms. US patent 8,603,514 B2. 2013 Dec 10.

133. Jacob S, Nair AB, Shah J. Orodispersible films: current innovations and emerging trends. Pharmaceutics. 2023;15(1):52. https://doi.org/10.3390/pharmaceutics15010052 PMid:36678681 PMCid:PMC9861000

134. Takeuchi Y, Kato T, Karasawa K. Orally disintegrating films: the effects of water content on mechanical properties. Int J Pharm X. 2021;3:100100. https://doi.org/10.1016/j.jddst.2021.102893

135. Janigová N, Elbl J, Pavloková S, Gajdziok J. Effects of various drying times on the properties of 3D-printed orodispersible films. Pharmaceutics. 2022;14(2):250. https://doi.org/10.3390/pharmaceutics14020250 PMid:35213983 PMCid:PMC8878870

136. Abbot V, Sharma P, Sharma A, Sharma D, Sharma T. Micelles transforming modern medicine: a comprehensive review on the role of micellar physicochemical properties in improving flavonoid bioavailability and neomycin efficacy. Discover Chemistry. 2025;2:220. https://doi.org/10.1007/s44371-025-00292-y

137. Varun S, Keerthy HS. Innovative strategies in the formulation and applications of mouth dissolving films for enhanced oral drug delivery. Drug Dev Ind Pharm. 2025; [Epub ahead of print]. https://doi.org/10.1080/03639045.2025.2510581 PMid:40411319

138. Reis CP, Neves AR, Segundo MA. Nanomedicine regulatory and safety challenges: lessons from current pharmaceutical development. Pharmaceutics. 2022;14(7):1449. https://doi.org/10.3390/pharmaceutics14071449 PMid:35890343 PMCid:PMC9323949

139. Sato H, Yamada K, Miyake M, Onoue S. Recent advancements in the development of nanocarriers for mucosal drug delivery systems to control oral absorption. Pharmaceutics. 2023;15(12):2708. https://doi.org/10.3390/pharmaceutics15122708 PMid:38140049 PMCid:PMC10747340

140. Hwang D, Ramsey JD, Kabanov AV. Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. Adv Drug Deliv Rev. 2020;156:80-118. https://doi.org/10.1016/j.addr.2020.09.009 PMid:32980449 PMCid:PMC8173698

141. Sosnik A. Polymeric micelles in mucosal drug delivery: challenges towards clinical translation. Biotechnol Adv. 2015;33(6):1818-1846. https://doi.org/10.1016/j.biotechadv.2015.01.003 PMid:25597531

142. Elbl J, Veselý M, Blaháčková D, Ondruš J, Kulich P, Mašková E, Mašek J, Gajdziok J. Development of 3D printed multi-layered orodispersible films with porous structure applicable as a substrate for inkjet printing. Pharmaceutics. 2023;15(2):714. https://doi.org/10.3390/pharmaceutics15020714 PMid:36840036 PMCid:PMC9961792

Published

2025-12-15
Statistics
Abstract Display: 169
PDF Downloads: 100
PDF Downloads: 28

How to Cite

1.
Cole KH, Modi P. Micelle-Loaded Oral Dissolvable Strips: A Novel Strategy to Enhance Bioavailability and Pharmacokinetics of Therapeutics. J. Drug Delivery Ther. [Internet]. 2025 Dec. 15 [cited 2026 Jan. 21];15(12):122-39. Available from: https://jddtonline.info/index.php/jddt/article/view/7441

How to Cite

1.
Cole KH, Modi P. Micelle-Loaded Oral Dissolvable Strips: A Novel Strategy to Enhance Bioavailability and Pharmacokinetics of Therapeutics. J. Drug Delivery Ther. [Internet]. 2025 Dec. 15 [cited 2026 Jan. 21];15(12):122-39. Available from: https://jddtonline.info/index.php/jddt/article/view/7441