Cubosome based Nanocarriers for Drug Delivery: Recent Advances, Clinical Translation, and Future Perspectives

Authors

  • Ankita Gadhave Department of Pharmaceutics, Shri Vishweshwar Shikshan Prasarak Mandal's, Shivlingeshwar College of Pharmacy, Almala Tq Ausa, Dist Latur, Maharashtra, India, 413.
  • Sameer Shafi Department of Pharmaceutics, Shri Vishweshwar Shikshan Prasarak Mandal's, Shivlingeshwar College of Pharmacy, Almala Tq Ausa, Dist Latur, Maharashtra, India, 413.
  • Waghmare Pranita Department of Pharmaceutics, Shri Vishweshwar Shikshan Prasarak Mandal's, Shivlingeshwar College of Pharmacy, Almala Tq Ausa, Dist Latur, Maharashtra, India, 413.
  • Swami Shivlila Department of Pharmaceutics, Shri Vishweshwar Shikshan Prasarak Mandal's, Shivlingeshwar College of Pharmacy, Almala Tq Ausa, Dist Latur, Maharashtra, India, 413.
  • Damane Madhuri Department of Pharmaceutics, Shri Vishweshwar Shikshan Prasarak Mandal's, Shivlingeshwar College of Pharmacy, Almala Tq Ausa, Dist Latur, Maharashtra, India, 413.
  • Harshada Salunke Department of Pharmaceutics, Shri Vishweshwar Shikshan Prasarak Mandal's, Shivlingeshwar College of Pharmacy, Almala Tq Ausa, Dist Latur, Maharashtra, India, 413.

DOI:

https://doi.org/10.22270/ajprd.v14i3.1833

Abstract

The bicontinuous cubic liquid crystalline phases are also being exploited as emerging lipid based nanocarriers, providing a novel three dimensional nanostructure with connected lipid bilayers and aqueous channels. This architecture allows the encapsulation of both hydrophilic, lipophilic and amphiphilic drugs with high loading, stability and controlled release properties. Cubosomes have been recently receiving a lot of attention in nanomedicine because of their bioavailability, drug stabilization, and therapeutic efficacy for various drug delivery platforms such as oral, topical, ocular, transdermal, pulmonary and parenteral delivery. With the development of formulation concepts (top down bottom up, hydrotrope dilution, solvent free and microfluidic technologies) their scalability and reproducibility have been enhanced. Furthermore, surface functionalization and stimuli responsive designs have facilitated targeted and theranostic uses in cancer therapy, neurological and ophthalmological diseases. These benefits are accompanied by manufacturing scale up, long term stability, regulatory issues and restricted clinical translation. Future studies will incorporate quality by design principles and advanced manufacturing techniques, which should help to expedite clinical development. Overall, cubosomes represent a versatile and promising platform for next generation drug delivery systems in precision nanomedicine.

 

Downloads

Download data is not yet available.

References

Larsson K. Cubic lipid-water phases: structures and biomembrane aspects. J Phys Chem. 1989;93(21):7304-7314.

Shah JC, Sadhale Y, Chilukuri DM. Cubic phase gels as drug delivery systems. Adv Drug Deliv Rev. 2001;47(2-3):229-250.

Spicer PT, Hayden KL, Lynch ML, Ofori-Boateng A, Burns JL. Novel process for producing cubic liquid crystalline nanoparticles (cubosomes). Langmuir. 2001;17(19):5748-5756.

Spicer PT. Cubosome processing: industrial nanoparticle technology development. Chem Eng Res Des. 2005;83(11):1283-1286.

Rizwan SB, Boyd BJ, Rades T, Hook S. Cubosomes: structure, preparation and use as an antigen delivery system. Expert Opin Drug Deliv. 2010; 7(10):1133-1144.

Negrini R, Mezzenga R. Diffusion, molecular separation, and drug delivery from lipid mesophases with tunable water channels. Langmuir. 2011; 27(9):5296-5303.

Yaghmur A, Mu H. Recent advances in drug delivery applications of cubosomes, hexosomes, and solid lipid nanoparticles. Acta Pharm Sin B. 2021; 11(4):871-885.

Chong JYR, Mulet X, Waddington LJ, Boyd BJ, Drummond CJ. Steric stabilizers for cubic phase nanoparticles (cubosomes): role of stabilizer concentration and molecular weight. Soft Matter. 2011; 7(10):4768-4777.

Barauskas J, Landh T. Phase behavior of the phytantriol/water system. Langmuir. 2003; 19(23):9562-9565.

Mezzenga R, Seddon JM, Drummond CJ, Boyd BJ, Schröder-Turk GE, Sagalowicz L. Nature-inspired design and application of lipidic lyotropic liquid crystals. Adv Mater. 2019;31(35):1900818.

Nazaruk E, Bilewicz R. Cubosomes as efficient nanocarriers for chemotherapeutics. ChemPlusChem. 2017; 82(4):570-575.

Abourehab MAS, Ansari MJ, Singh A, Hassan A, Abdelgawad MA, Shrivastav P, et al. Cubosomes as an emerging platform for drug delivery: a review of the state of the art. J Mater Chem B. 2022;10(15):2781-2819.

Miranda I, Misra B, Manjunath MC, Nayak G, Likhitha U, Nayak UY. Responsive nano-structured cubosomes: advancements and therapeutic applications. Adv Pharm Bull. 2025;15(2):284-292.

Sivadasan D, Sultan MH, Alqahtani SS, Javed S, Aldawsari MF, Badr-Eldin SM. Cubosomes in drug delivery: a comprehensive review on structural components, preparation techniques and therapeutic applications. Biomedicines. 2023;11(4):1114.

Bhatt AH, Patel HK, Shah NR, Patel VP. Cubosomes in non-oral drug delivery: advancing precision therapeutics from bench to bedside. Int J Pharm. 2025;673:125678.

Barriga HMG, Holme MN, Stevens MM. Cubosomes: the next generation of smart lipid nanoparticles? Angew Chem Int Ed Engl. 2019;58(10):2958-2978.

Szlezak M, Nieciecka D, Joniec A, et al. Monoolein cubic phase gels and cubosomes doped with magnetic nanoparticles: hybrid materials for controlled drug release. ACS Appl Mater Interfaces. 2017;9(3):2796-2805.

International Council for Harmonisation. ICH Q8(R2): Pharmaceutical Development. Geneva: ICH; 2009.

International Council for Harmonisation. ICH Q9: Quality Risk Management. Geneva: ICH; 2020.

International Council for Harmonisation. ICH Q10: Pharmaceutical Quality System. Geneva: ICH; 2008.

Almoshari Y. Development, therapeutic evaluation and theranostic applications of cubosomes on cancers: an updated review. Pharmaceutics. 2022; 14(3):600.

Cai X, Refaat A, Gan PY, Fan B, Yu H, Thang SH, et al. Angiopep-2-functionalized lipid cubosomes for blood-brain barrier crossing and glioblastoma treatment. ACS Appl Mater Interfaces. 2024; 16(10):12161-12174.

Fong WK, Hanley T, Boyd BJ. Stimuli responsive liquid crystals provide on-demand drug delivery in vitro and in vivo. J Control Release. 2009; 135(3):218-226.

Bryant SJ, Bathke EK, Edler KJ. Bottom-up cubosome synthesis without organic solvents. J Colloid Interface Sci. 2021;601:98-105.

Mohammad Y, Prentice RN, Boyd BJ, Rizwan SB. Comparison of cubosomes and hexosomes for brain drug delivery. J Colloid Interface Sci. 2022; 605:146-154.

Gadhave A, Shafi S, Madhuri D, Waghmare P, Shivlila S. Cubosomes as a next generation innovative nanocarriers: from structural engineering to therapeutic frontiers. Int J Creat Res Thoughts. 2025;13(10):1-11.

Bessone CDV, Akhlaghi SP, Tártara LI, Quinteros DA, Loh W, Allemandi DA. Latanoprost-loaded phytantriol cubosomes for glaucoma. Eur J Pharm Sci. 2021; 160:105748.

Alhakamy NA, Hosny KM, Rizg WY, et al. Hyaluronic acid-poloxamer in situ gel loaded with voriconazole cubosomes for ocular delivery. Gels. 2022;8(4):241.

Chen Z, Huang Q, Song Y, et al. Cubosomes-assisted transdermal delivery of doxorubicin and indocyanine green for melanoma therapy. Biomed Pharmacother. 2023;166:115316.

Yaghmur A, Moghimi SM. Intrinsic and dynamic heterogeneity of nonlamellar lyotropic liquid crystalline nanodispersions. ACS Nano. 2023;17(22):22183-22195.

Chavda VP, Dyawanapelly S, Dawre S, et al. Lyotropic liquid crystalline phases: drug delivery and biomedical applications. Int J Pharm. 2023;647:123546.

Umar H, Wahab HA, Gazzali AM, et al. Cubosomes: design, development, and tumor-targeted drug delivery applications. Polymers (Basel). 2022;14(15):3118.

Oliveira C, Ferreira CJO, Sousa M, et al. Cubosomes: characterization and applications. Nanomaterials (Basel). 2022;12(13):2224.

Umar H, Wahab HA, Ahmed N, et al. Cisplatin-loaded cubosomes for lung carcinoma. Drug Dev Ind Pharm. 2025;51(9):1002-1015.

Villalva DG, França CG, Loh W. Cubosomes in hyaluronic acid hydrogel for diclofenac delivery. Colloids Surf B Biointerfaces. 2022;212:112352.

Gadhave A, Shafi S, Shivlila S, Waghmare P, Damane M. Green-synthesized cubosomes: sustainable nanotechnology approach. Eur J Biomed Pharm Sci. 2025;12(12):298-302.

Zaker H, Taymouri S, Mostafavi A. Azithromycin-loaded cubosomes formulation. Res Pharm Sci. 2023;18(1):49-58.

Elfaky MA, Sirwi A, Tolba HH, et al. Ketoconazole cubic liquid crystalline nanoparticles for ocular delivery. J Pharm Sci. 2021;110(5):2210-2220.

Published

2026-06-19

How to Cite

Ankita Gadhave, Sameer Shafi, Waghmare Pranita, Swami Shivlila, Damane Madhuri, & Harshada Salunke. (2026). Cubosome based Nanocarriers for Drug Delivery: Recent Advances, Clinical Translation, and Future Perspectives. Asian Journal of Pharmaceutical Research and Development, 14(3), 511–521. https://doi.org/10.22270/ajprd.v14i3.1833