Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Cubosome: A Potential Liquid Crystalline Carrier System

Author(s): Pragya Sharma, Surbhi Dhawan and Sanju Nanda*

Volume 26 , Issue 27 , 2020

Page: [3300 - 3316] Pages: 17

DOI: 10.2174/1381612826666200617162424

Price: $65


Cubosome is a biocompatible, thermodynamically stable and bioadhesive drug carrier that is prepared from certain amphiphilic lipids and surfactants when mixed in a definite ratio. Structurally, they are selfassembled nano-constructed liquid crystalline particles comprising three-dimensionally arranged bicontinuous as well as nonintersecting lipid bilayers that give them a honeycomb-like appearance. Morphological characterization through SAXS (small-angle X-ray scattering) and cryo-TEM (cryo-transmission electron microscopy) revealed that they are square and round shaped particles in the nanometer range. These carriers have two separate aqueous regions and a large interfacial area that allow them to carry a variety of bioactive molecules having hydrophobic, hydrophilic or amphiphilic behavior.

One of either two strategies i.e., top-down or bottom-up methods can be adopted to prepare these cubic structures. A number of dispersion techniques like sonication, spray drying, high-pressure homogenization or spontaneous emulsification can be adopted to prepare cubosomes. Their characteristics and benefits like multicompartmental structure, high drug loading, simple and convenient method of preparation, use of biodegradable lipids such as glycerol monooleate, encapsulation of hydrophilic, hydrophobic and amphiphilic moieties, targeted and controlled release make them versatile bioactive carriers that can be administered through multiple biological routes like topical, transdermal, parenteral, and oral. Cubosomes have appreciable applications in various fields especially in the pharmaceutical industry where they are used as potential bioactive carriers. Molecules like paclitaxel, oligonucleotide, δ-amino-levulinic acid, bovine serum albumin, etc. can be easily delivered through this system.

This article provides a detailed note on the structure of cubosomes, ingredients and techniques used for their preparation, mechanism of drug release, applications and routes of drug administration, their formulations, patent review and market scenario.

Keywords: Liquid crystalline structures, cubic phase, top-down and bottom-up techniques, monoleins, surfactants, routes, patent, formulations.

Shrestha H, Bala R, Arora S. Lipid-Based Drug Delivery Systems. J Pharm (Cairo) 2014; 2014801820
[]] [PMID: 26556202]
Rakotoarisoa M, Angelov B, Garamus VM, Angelova A. Curcumin- and Fish Oil-Loaded Spongosome and Cubosome Nanoparticles with Neuroprotective Potential against H2O2-Induced Oxidative Stress in Differentiated Human SH-SY5Y Cells. ACS Omega 2019; 4: 3061-73.
Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 2002; 54(5): 631-51.
Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003; 55(3): 329-47.
[] [PMID: 12628320]
Gershkovich P, Wasan KM, Barta CA. A review of the application of lipid-based systems in systemic, dermal/transdermal, and ocular drug delivery. Crit Rev Ther Drug Carrier Syst 2008; 25(6): 545-84.
[] [PMID: 19166393]
Pavelić Z, Škalko-Basnet N, Filipović-Grcić J, Martinac A, Jalšenjak I. Development and in vitro evaluation of a liposomal vaginal delivery system for acyclovir. J Control Release 2005; 106(1-2): 34-43.
[] [PMID: 15979189]
Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 2002; 54(1)(Suppl. 1): S131-55.
[] [PMID: 12460720]
Sadhu VR, Beram NS, Kantamneni P. A review on cubosome: The novel drug delivery system. GSC Biological and Pharmaceutical Sciences 2018; 5(1): 76-81.
Yu C, Gao C, Lü S, et al. Facile preparation of pH-sensitive micelles self-assembled from amphiphilic chondroitin sulfate-histamine conjugate for triggered intracellular drug release. Colloids Surf B Biointerfaces 2014; 115: 331-9.
[] [PMID: 24398081]
Liu Z, Dong C, Wang X, et al. Self-assembled biodegradable protein-polymer vesicle as a tumor-targeted nanocarrier. ACS Appl Mater Interfaces 2014; 6(4): 2393-400.
[] [PMID: 24456410]
Garti N, Libster D, Aserin A. Lipid polymorphism in lyotropic liquid crystals for triggered release of bioactives. Food Funct 2012; 3(7): 700-13.
[] [PMID: 22592749]
Zhen G, Hinton TM, Muir BW, et al. Glycerol monooleate-based nanocarriers for siRNA delivery in vitro. Mol Pharm 2012; 9(9): 2450-7.
[] [PMID: 22794355]
Chang DP, Barauskas J, Dabkowska AP, Wadsäter M, Tiberg F, Nylander T. Non-lamellar lipid liquid crystalline structures at interfaces. Adv Colloid Interface Sci 2015; 222: 135-47.
[] [PMID: 25435157]
Angelova A, Angelov B, Drechsler M, Garamus VM, Lesieur S. Protein entrapment in PEGylated lipid nanoparticles. Int J Pharm 2013; 454(2): 625-32.
[] [PMID: 23791734]
Mai CH, Diep TT, Le TTT, Nguyen V. Advances in colloidal dispersions: A review. J Dispers Sci Technol 2019.
Larsson K. Two cubic phases in monoolein-water system. Nature 1983; 304(5927): 664.
Thadanki M, Kumari PS, Prabha KS. Overview of Cubosomes: a nano particle. Int J Res Pharm Chem 2011; 1(3): 535-41.
Rakotoarisoa M, Angelov B, Espinoza S, Khakurel K, Bizien T, Angelova A. Cubic Liquid Crystalline nanostructures involving catalase and curcumin: BioSAXS study and catalase peroxidatic function after Cubosomal nanoparticle treatment of differentiated SH-SY5Y Cells. Molecules 2019; 24(17): 1-21.
[] [PMID: 31443533]
Rajabalaya R, Musa MN, Kifli N, David SR. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals. Drug Des Devel Ther 2017; 11: 393-406.
[] [PMID: 28243062]
Guo C, Wang J, Cao F, Lee RJ, Zhai G. Lyotropic liquid crystal systems in drug delivery. Drug Discov Today 2010; 15(23-24): 1032-40.
[] [PMID: 20934534]
Longley W, Mcintosh TJ. A bicontinuous tetrahedral structure in a liquid-crystalline lipid. Nature 1983; 303: 612-4.
Montis C, Castroflorio B, Mendozza M, Salvatore A, Berti D, Baglioni P. Magnetocubosomes for the delivery and controlled release of therapeutics. J Colloid Interface Sci 2015; 449: 317-26.
[] [PMID: 25533536]
Murgia S, Falchi AM, Meli V, et al. Cubosome formulations stabilized by a dansyl-conjugated block copolymer for possible nanomedicine applications. Colloids Surf B Biointerfaces 2015; 129: 87-94.
[] [PMID: 25829131]
Lutton ES. Phase behavior of aqueous systems of monoglycerides. J Am Oil Chem Soc 1965; 42(12): 1068-70.
[] [PMID: 5845647]
Kulkarni CV, Wachter W, Iglesias-Salto G, Engelskirchen S, Ahualli S. Monoolein: a magic lipid? Phys Chem Chem Phys 2011; 13(8): 3004-21.
[] [PMID: 21183976]
Karami Z, Hamidi M. Cubosomes: remarkable drug delivery potential. Drug Discov Today 2016; 21(5): 789-801.
[] [PMID: 26780385]
Garg G, Saraf S, Saraf S. Cubosomes: an overview. Biol Pharm Bull 2007; 30(2): 350-3.
[] [PMID: 17268078]
Boyd BJ, Whittaker DV, Khoo SM, Davey G. Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems. Int J Pharm 2006; 309(1-2): 218-26.
[] [PMID: 16413980]
Barauskas J, Landh T. Phase behavior of the phytantriol/water system. Langmuir 2003; 19: 9562-5.
Rizwan SB, Dong YD, Boyd BJ, Rades T, Hook S. Characterisation of bicontinuous cubic liquid crystalline systems of phytantriol and water using cryo field emission scanning electron microscopy (cryo FESEM). Micron 2007; 38(5): 478-85.
[] [PMID: 17011783]
Rizwan SB, McBurney WT, Young K, et al. Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses. J Control Release 2013; 165(1): 16-21.
[] [PMID: 23142776]
Jain S, Bhankur N, Swarnakar NK, Thanki K. Phytantriol based stealth lyotropic liquid crystalline nanoparticles for improved antitumor efficacy and reduced toxicity of docetaxel. Pharm Res 2015; 32(10): 3282-92.
[] [PMID: 25968624]
Rizwan SB, Assmus D, Boehnke A, et al. Preparation of phytantriol cubosomes by solvent precursor dilution for the delivery of protein vaccines. Eur J Pharm Biopharm 2011; 79(1): 15-22.
[] [PMID: 21237267]
Dong YD, Dong AW, Larson I, et al. Impurities in commercial phytantriol significantly alter its lyotropic liquid-crystalline phase behavior. Langmuir 2008; 24(13): 6998-7003.
[] [PMID: 18522450]
Guillot S, Salentinig S, Chemelli A, Sagalowicz L, Leser ME, Glatter O. Influence of the stabilizer concentration on the internal liquid crystalline order and the size of oil-loaded monolinolein-based dispersions. Langmuir 2010; 26(9): 6222-9.
[] [PMID: 20143786]
Chong JYT, Mulet X, Boyd BJ, Drummond CJ. Chapter five - steric stabilizers for cubic phase lyotropic liquid crystal nanodispersions (Cubosomes). Adv Planar Lipid Bilayers Liposomes 2015; 21: 131-87.
Dong YD, Larson I, Barnes TJ, et al. Understanding the interfacial properties of nanostructured liquid crystalline materials for surface-specific delivery applications. Langmuir 2012; 28(37): 13485-95.
[] [PMID: 22889049]
Zhai J, Waddington L, Wooster TJ, Aguilar MI, Boyd BJ. Revisiting β-casein as a stabilizer for lipid liquid crystalline nanostructured particles. Langmuir 2011; 27(24): 14757-66.
[] [PMID: 22026367]
Chong JYT, Mulet X, Waddington LJ, Boyd BJ, Drummond CJ. High-throughput discovery of novel steric stabilizers for cubic lyotropic liquid crystal nanoparticle dispersions. Langmuir 2012; 28(25): 9223-32.
[] [PMID: 22630595]
Uyama M, Nakano M, Yamashita J, Handa T. Useful modified cellulose polymers as new emulsifiers of cubosomes. Langmuir 2009; 25(8): 4336-8.
[] [PMID: 19296640]
Zhai J, Hinton TM, Waddington LJ, et al. Lipid-PEG conjugates sterically stabilize and reduce the toxicity of phytantriol-based lyotropic liquid crystalline nanoparticles. Langmuir 2015; 31(39): 10871-80.
[] [PMID: 26362479]
Angelov B, Angelova A, Filippov SK, et al. DNA/fusogenic lipid nanocarrier assembly: millisecond structural dynamics. J Phys Chem Lett 2013; 4(11): 1959-64.
[] [PMID: 26283134]
Sri VR, Reddy AM, Karthikeyan R, Srinivasababu P. A review on: Cubosomes drug delivery system. Indian J Drugs 2017; 5(3): 104-8.
Bachhav1 JK, Bhairav BA, Saudagar RB. Cubosomal technique: a review. Int J Pharm Tech 2015; 7(2): 3263-72.
Um JY, Chung H, Kim KS, Kwon IC, Jeong SY. In vitro cellular interaction and absorption of dispersed cubic particles. Int J Pharm 2003; 253(1-2): 71-80.
[] [PMID: 12593938]
Tilekar KB, Khade PH, Shitole MH, Jograna MB, Patil RY. Cancer oriented Cubosomes -A review. Int J Pharm Res Scholars 2014; 3(4): 198-209.
Muir BW, Zhen G, Gunatillake P, Hartley PG. Salt induced lamellar to bicontinuous cubic phase transitions in cationic nanoparticles. J Phys Chem B 2012; 116(11): 3551-6.
[] [PMID: 22360659]
Hartnett TE, Ladewig K, O’Connor AJ, Hartley PG, McLean KM. Size and phase control of cubic lyotropic liquid crystal nanoparticles. J Phys Chem B 2014; 118(26): 7430-9.
[] [PMID: 24915497]
Enriquez J, Goldberg R. Transforming Life, Transforming Business: The Life-Science Revolution. Harv Bus Rev 2000; 96-104.
Ribier A, Biatry B. inventor; LOreal SA, assignee Cosmetic and dermatologic composition comprising a stable aqueous dispersion of phytantriol-based gel particles containing a long-chain surfactant as dispersant and stabilizer European Patent Office EP 0686386A1, 1995 Dec
Ribier A, Biatry B. Cosmetic or Dermatologic Oil/ Water Dispersion Stabilized with Cubic Gel Particles and Method of Preparation European Patent Office EP0 711 540A1. 1996, May.
Spicer PT, Small WB II, Lynch ML. Cubic Liquid Crystalline Compositions and Methods for their Preparation Patent Cooperation Treaty WO 2002066014A2., 2002.Aug
Kala D, Aiswarya CS. Cubosomes-A novel drug delivery system and its functionalisation. World J Pharm Pharm Sci 2017; 6(3): 286-300.
Pagar RY, Vaishnav SP, Bairagi VA. Cubosome: Innovative nanostructures for drug delivery. Pharma Sci Monitor 2018; 9(1): 97-107.
Nanjwade BK, Hundekar YR, Kamble MS, Srichana T. Development of Cuboidal Nanomedicine by Nanotechnology. Austin J Nanomed Nanotechnol 2014; 2(4): 1023.
Upadhye SS, Kothali BK, Apte AK, Kulkarni AA, Khot VS. A Review on Cubosomes. Am J Pharm Tech Res 2017; 7(4): 21-35.
Tilekar K, Khade P, Kakade S, Kotwal S, Patil R. Cubosomes-A Drug delivery system. Int J Pharm Chem Biol Sci 2014; 4(4): 812-24.
Zhai J, Fong C, Tran N, Drummond CJ. Non-Lamellar Lyotropic Liquid Crystalline Lipid Nanoparticles for the Next Generation of Nanomedicine. ACS Nano 2019; 13(6): 6178-206.
[] [PMID: 31082192]
Molly BA, Prasanthi NL. Cubic liquid crystalline nanoparticles (Cubosomes): A novel carrier for drug delivery. Int J Pharm Sci Res 2019; 10(3): 973-84.
Otte A, Soh BK, Yoon G, Park K. Liquid crystalline drug delivery vehicles for oral and IV/subcutaneous administration of poorly soluble (and soluble) drugs. Int J Pharm 2018; 539(1-2): 175-83.
[] [PMID: 29371020]
Omar SM, Ismail A, Hassanin KD, Dawoud SH. Formulation and Evaluation of Cubosomes as Skin Retentive System for Topical Delivery of Clotrimazole. J Adv Pharm Educ Res 2019; 3(2): 68-82.
El-Laithy HM, Badawi A, Abdelmalak NS, El-Sayyad N. Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine. Chem Pharm Bull (Tokyo) 2018; 66(12): 1165-73.
[] [PMID: 30232306]
Reddy KV, Reddy MS, Ul Haq SMF. Formulation and Evaluation of Gastro Retentive In-Situ Floating Gels of Irbesartan Cubosomes. Int J Res Advent Technol 2018; 6(11): 3232-41.
Hashem F, Nasr M, Youssif M. Formulation and Characterization of Cubosomes Containing REB for Improvement of Oral Absorption of the Drug in Human Volunteers. J Adv Pharm Educ Res 2018; 2(2): 95-103.
Bachhav JK, Bhairav BA, Saudagar RB. Formulation and Evaluation of topical Emulgel of Ketoconazole by Cubosomal technique. World J Pharm Res 2017; 6(10): 567-88.
Daware SU, Saudagar RB. Formulation and development of Cubosomes loaded Emulgel of Fluconazole. Eur J Biomed Pharm Sci 2017; 4(11): 321-31.
Ali MA, Kataoka N, Ranneh AH, et al. Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes. Chem Pharm Bull (Tokyo) 2017; 65(1): 42-8.
[] [PMID: 28049915]
Nasr M, Dawoud M. Sorbitol Based Powder Precursor of Cubosomes as an Oral Delivery System for Improved Bioavailability of Poorly Water-Soluble Drugs. J Drug Deliv Sci Technol 2016; 35: 106-13.
Kadhum WR, Oshizaka T, Ichiro H, Todo H, Sugibayashi K. Usefulness of liquid-crystal oral formulations to enhance the bioavailability and skin tissue targeting of p-amino benzoic acid as a model compound. Eur J Pharm Sci 2016; 88: 282-90.
[] [PMID: 27072433]
Ali Z, Sharma PM, Warsi MH. Fabrication and Evaluation of Ketorolac Loaded Cubosome for Ocular Drug Delivery. J Appl Pharm Sci 2016; 6(09): 204-8.
Rarokar NR, Saoji SD, Raut NA, Taksande JB, Khedekar PB, Dave VS. Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel. AAPS PharmSciTech 2016; 17(2): 436-45.
[] [PMID: 26208439]
Thakkar V, Korat V, Baldaniya L, Gohel M, Gandhi T, Patel N. Development and characterization of novel hydrogel containing antimicrobial drug for treatment of burns. Int J Pharm Investig 2016; 6(3): 158-68.
[] [PMID: 27606259]
Peng X, Zhou Y, Han K, et al. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin. Drug Des Devel Ther 2015; 9: 4209-18.
[] [PMID: 26345516]
Nasr M, Ghorab MK, Abdelazem A. In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting. Acta Pharm Sin B 2015; 5(1): 79-88.
[] [PMID: 26579429]
Sharma R, Kaur G, Kapoor DN. Fluconazole Loaded Cubosomal Vesicles for Topical Delivery. Int J Drug Dev & Res 2015; 7(3): 32-41.
Khalifa MKA. Miconazole Nitrate based cubosome hydrogels for topical application. Int J Drug Deliv 2015; 7(1): 1-12.
Zhang Y, Zhang K, Guo T, Li Y, Zhu C, Feng N. Transdermal baicalin delivery using diethylene glycol monoethyl ether-mediated cubic phase gel. Int J Pharm 2015; 479(1): 219-26.
[] [PMID: 25543112]
Abdelrahman FE, Elsayed I, Gad MK, Badr A, Mohamed MI. Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution. Int J Pharm 2015; 490(1-2): 281-91.
[] [PMID: 26026251]
Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY. Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer’s disease: pharmaceutical, biological, and toxicological studies. Int J Nanomedicine 2015; 10: 5459-73.
[] [PMID: 26346130]
Kwon TK, Kim JC. Preparation and In Vitro Skin Permeation of Cubosomes Containing Hinokitiol. J Dispers Sci Technol 2010; 31(7): 1004-9.
Venkatesh B, Indira S, Srinivas P. Formulation and evaluation of miconazole nitrate as a cubosomal topical gel. J Glob Trends Pharm Sci 2014; 5(4): 2037-47.
Yang Z, Chen M, Yang M, Chen J, Fang W, Xu P. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection. Int J Nanomedicine 2014; 9: 327-36.
[PMID: 24421641]
Hundekar YR, Saboji JK, Patil SM, Nanjwade BK. Preparation and Evaluation of Diclofenac sodium Cubosomes for percutaneous administration. World J Pharm Pharm Sci 2014; 3(5): 523-39.
Li J, Wu L, Wu W, et al. A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate. Int J Pharm 2013; 455(1-2): 75-84.
[] [PMID: 23916822]
Wu W, Li J, Wu L, et al. Ophthalmic delivery of brinzolamide by liquid crystalline nanoparticles: in vitro and in vivo evaluation. AAPS PharmSciTech 2013; 14(3): 1063-71.
[] [PMID: 23813437]
Praca FSG, Medina WSG, Petrilli R, Bentley M. Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration. Curr Nanosci 2012; 8: 535-40.
Esposito E, Mariani P, Ravani L, et al. Nanoparticulate lipid dispersions for bromocriptine delivery: characterization and in vivo study. Eur J Pharm Biopharm 2012; 80(2): 306-14.
[] [PMID: 22061262]
Gong X, Moghaddam MJ, Sagnella SM, Conn CE, Mulet X, Danon SJ, et al. Nanostructured Self-Assembly Materials from Neat and Aqueous Solutions of C18 Lipid Pro-Drug Analogues of Capecitabine- A Chemotherapy Agent. Focus on Nanoparticulate Cubosomes of the Oleyl Analogue. Soft Matter 2011; 7: 5764-76.
Nguyen TH, Hanley T, Porter CJH, Boyd BJ. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration. J Control Release 2011; 153(2): 180-6.
[] [PMID: 21497623]
Han IH, Choi SU, Nam DY, et al. Identification and assessment of permeability enhancing vehicles for transdermal delivery of glucosamine hydrochloride. Arch Pharm Res 2010; 33(2): 293-9.
[] [PMID: 20195831]
Gan L, Han S, Shen J, et al. Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: Improving preocular retention and ocular bioavailability. Int J Pharm 2010; 396(1-2): 179-87.
[] [PMID: 20558263]
Han S, Shen JQ, Gan Y, et al. Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability. Acta Pharmacol Sin 2010; 31(8): 990-8.
[] [PMID: 20686524]
Cervin C, Tinzl M, Johnsson M, Abrahamsson PA, Tiberg F, Dizeyi N. Properties and effects of a novel liquid crystal nanoparticle formulation of docetaxel in a prostate cancer mouse model. Eur J Pharm Sci 2010; 41(2): 369-75.
[] [PMID: 20633647]
Couvreur P, Reddy LH, Mangenot S, et al. Discovery of new hexagonal supramolecular nanostructures formed by squalenoylation of an anticancer nucleoside analogue. Small 2008; 4(2): 247-53.
[] [PMID: 18247384]
Lopes LB, Ferreira DA, de Paula D, et al. Reverse hexagonal phase nanodispersion of monoolein and oleic acid for topical delivery of peptides: in vitro and in vivo skin penetration of cyclosporin A. Pharm Res 2006; 23(6): 1332-42.
[] [PMID: 16715364]
Johnsson M, Barauskas J, Norlin A, Tiberg F. Physicochemical and drug delivery aspects of lipid-based liquid crystalline nanoparticles: a case study of intravenously administered propofol. J Nanosci Nanotechnol 2006; 6(9-10): 3017-24.
[] [PMID: 17048513]
Esposito E, Cortesi R, Drechsler M, et al. Cubosome dispersions as delivery systems for percutaneous administration of indomethacin. Pharm Res 2005; 22(12): 2163-73.
[] [PMID: 16267633]
Chung H, Kim J, Um JY, Kwon IC, Jeong SY. Self-assembled “nanocubicle” as a carrier for peroral insulin delivery. Diabetologia 2002; 45(3): 448-51.
[] [PMID: 11914752]
Mulet X, Szto GYF, Kannar D. inventor; Zeenar Enterprises Pty Ltd, assignee Niacin formulation United States patent US 010335403B2. 2019, Jul.
Bromley PJ, Rahim N, Lam KJ. inventor; Virun, Inc, assignee Compositions for providing agents that degrade in water United States patent US 10213490B2. , 2019.Feb
Joabsson F, Tiberg F, Johnsson M. inventor; Camurus Ab, assignee Method for loading amphiphile particles with active agents United States patent US 9067190B2., 2015.Jun
Joabsson F, Johnsson M, Norlin A, Tiberg F. inventor; Camurus Ab, assignee Somatostatin analogue formulations United States patent US 8871712B2., 2014.Oct
Ikeda Y, Yamashita J, Hijikuro I, Imuta S, Hiroki Y, Takahashi T. inventor; Chemgenesis Incorporated, assignee Low-viscosity liquid crystal compound United States patent US 8703922B2. , 2014.Apr
Joabsson F, Tiberg F. inventor; Camurus Ab, assignee Compositions of lipids and cationic peptides United States patent US 8865021B2. , 2014.Oct
Johnsson M, Joabsson F, Tiberg F. inventor; Camurus Ab, assignee Compositions forming non-lamellar dispersions United States patent US 8541400B2., 2013.Sept
Drummond CJ, Sagnella SM, Moghaddam MJ, Gong X. inventor; Commonwealth Scientific and Industrial Research Organisation, assignee Amphiphile prodrugs United States patent US 8603999B2. , 2013.Dec
Anderson D. inventor; Lyotropic Therapeutics, Inc, assignee Stabilized uncoated particles of reversed liquid crystalline phase materlals United States patent US 8128905B2., 2012.Mar
Barauskas J, Tiberg F. inventor; Camurus Ab, assignee Nonlamellar compositions of DOPE and P80 United States patent US 8187629B2. , 2012.May
Perricone NV. inventor; Transdermal Biotechnology Inc, assignee Topical drug delivery using phosphatdylcholine United States patent US 8273711B2, 2012.Sept
Anderson D, Cameransi B. inventor; Lyotropic Therapeutics, Inc, assignee Drug-delivery vehicles based on reversed liquid crystalline phase materials European Patent EP 1677730B1., 2010.Dec
Hatoh M, Fujita Y, Ota T, Tanomura M, Shiono M. inventor; National Institute of Advanced Industrial Science and Technology, Kuraray Co, Ltd, Cytopathfinder, Inc, assignee Type II cubic liquid crystal composition United States patent US 7846903B2., 2010.Dec
Reszka R, Schluter R. inventor; Max DelbrueckCenter for Molecular Medicine, assignee Implantable active ingredient depot United States patent US 7556827B1., 2009.Jul
Anderson D. inventor; Lyotropic Therapeutics, Inc, assignee Particles with improved solubilization capacity United States patent US 6991809B2., 2006.Jan
Anderson D. inventor; Lyotropic Therapeutics, Inc, assignee Coated particles, methods of making and using United States patent US 6989195B2., 2006.Jan
Spicer PT, Small WB II, Lynch ML. inventor; Procter & Gamble Company, assignee Cubic liquid crystalline compositions and methods for their preparation United States patent US 7008646B2. , 2006.Mar
Lynch ML, Spicer PT. inventor; Procter and Gamble Company, assignee Functionalized cubic liquid crystalline phase materials and methods for their preparation & use United States patent US 6936187B2, 2005.Aug
Hansen J, Nielsen LS. inventor; GS Development ab, assignee Use of fatty acid esters as boadhesive substances United States patent US 6228383B1. 2001, May.
Ribier A, Biatry B. inventor; L’Oreal Paris, assignee Oily phase in aqueous phase dispersion stabilized by cubc gel particles and method of making United States patent US 6071524A. 2000, Jun.
Kawada I, Sakurai K, Tokoro K. inventor; Takasago International Corporation, assignee lipid composition containing a liquid crystal phase United States patent US 5916578A. 1999, Jun.
Ribier A, Biatry B. inventor; L’Oreal Paris, assignee Oily phase in aqueous phase dispersion stabilized by cubc gel particles and method of making United States patent US 5756108A. 1998, May.
Landh T, Larsson K. inventor; Gs Biochem Ab, assignee Particles, method of preparing said particles and uses thereof United States patent US 5531925A., 1996.Jul
Engstrom S, Lindman B, Larsson K. inventor; Fluid-Carbon International AB, assignee Method of preparing controlled-release preparations for biologically active materials and resulting compositions United States patent US 5151272A, 1992.Sept
Rao SV, Sravya BN, Padmalatha K. a review on cubosome: the novel drug delivery system. gsc biol pharm sci 2018; 05(01): 076-08.
Lakshmi NM, Yalavarthi PR, Vadlamudi HC, Thanniru J, Yaga Gk H. Cubosomes as targeted drug delivery systems - a biopharmaceutical approach. Curr Drug Discov Technol 2014; 11(3): 181-8.
[]] [PMID: 24836404]
Ali MZ, Warsi MH, Muheem A, Jahangir MA. Parvez1 N, Sharma PK. Cubic Liquid Nanocrystal system for drug delivery: A State of the art. World J Pharm Pharm Sci 2016; 5(1): 379-95.
Thomas A, Varghese J, Raju SP, Das C, Abraham E. Cubosomes-A novel drug delivery system. J Glob Trends Pharm Sci 2017; 8(4): 4718-27.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy