Skip to content
2000
image of Bigels as Novel Drug Delivery Systems: A Systematic Review on Efficiency and Influential Factors

Abstract

Background

Bigles are novel formulation merging two phase of hydrogel and organogel revealing dual properties to release active agents based on their lipophilic or hydrophilic nature.

Methods

A systematic search was conducted in PubMed, Scopus, and ISI Web of Science to find eligible studies evaluating the efficiency of bigels in drug release. 20 articles were included in the analysis based on the defined criteria.

Results

The results indicated that several different natural materials were used for bigel making. Span (52.38%) and Sunflower oil (23.80%) were the most solvents used for organogel formation. Also, gelatin, agar, gums, and other types of biopolymer were used as hydroglators. Most research (33.33%) focused on the release of metronidazole from bigel structure. Also, the range of drug release rates was 1.59 - 100% and in 42.85% of studies was >90%. The nature, content, and properties of both organogel and hydrogel and some process variables such as temperature, mixing speed and storage conditions were highlighted as the main influential factors on bigel formation and its bioactivity.

Conclusion

Bigels are an innovative structure that provides desired physicochemical and rheological properties for industrial applications. Excellent biocompatibility and / results have been documented for developed bigels. In this regard, an optimal preparation method is very important to show superior therapeutic effects.

Loading

Article metrics loading...

/content/journals/crcep/10.2174/0127724328288796240906040927
2024-10-30
2024-11-26
Loading full text...

Full text loading...

References

  1. Mao L. Lu Y. Cui M. Miao S. Gao Y. Design of gel structures in water and oil phases for improved delivery of bioactive food ingredients. Crit. Rev. Food Sci. Nutr. 2020 60 10 1651 1666 10.1080/10408398.2019.1587737 30892058
    [Google Scholar]
  2. Zhu Q. Gao J. Han L. Han K. Wei W. Wu T. Li J. Zhang M. Development and characterization of novel bigels based on monoglyceride-beeswax oleogel and high acyl gellan gum hydrogel for lycopene delivery. Food Chem. 2021 365 130419 10.1016/j.foodchem.2021.130419 34247047
    [Google Scholar]
  3. Singh V.K. Anis A. Banerjee I. Pramanik K. Bhattacharya M.K. Pal K. Preparation and characterization of novel carbopol based bigels for topical delivery of metronidazole for the treatment of bacterial vaginosis. Mater. Sci. Eng. C 2014 44 151 158 10.1016/j.msec.2014.08.026 25280691
    [Google Scholar]
  4. Hashemi B. Varidi M. Jafari S.M. Fabrication and characterization of novel whey protein-based bigels as structured materials with high-mechanical properties. Food Hydrocoll. 2023 145 109082 10.1016/j.foodhyd.2023.109082
    [Google Scholar]
  5. Francavilla A. Corradini M.G. Joye I.J. Bigels as delivery systems: Potential uses and applicability in food. Gels 2023 9 8 648 10.3390/gels9080648 37623103
    [Google Scholar]
  6. Chen Z. Bian F. Cao X. Shi Z. Meng Z. Novel bigels constructed from oleogels and hydrogels with contrary thermal characteristics: Phase inversion and 3D printing applications. Food Hydrocoll. 2023 134 108063 10.1016/j.foodhyd.2022.108063
    [Google Scholar]
  7. Yang J. Fu Y. Zheng H. Jia Y. Gao Y. Yin S. Mao L. Structural design of oleogel‐hydrogel bigels for co‐delivery of curcumin and epigallocatechin gallate with synergistic stability and bioactivity. Adv. Mater. Technol. 2023 8 14 2202185 10.1002/admt.202202185
    [Google Scholar]
  8. Behera B. Sagiri S.S. Pal K. Pramanik K. Rana U.A. Shakir I. Anis A. Sunflower oil and protein-based novel bigels as matrices for drug delivery applications—characterization and in vitro antimicrobial efficiency. Polym. Plast. Technol. Eng. 2015 54 8 837 850 10.1080/03602559.2014.974268
    [Google Scholar]
  9. Shakeel A. Lupi F.R. Gabriele D. Baldino N. De Cindio B. Bigels: A unique class of materials for drug delivery applications. Soft Mater. 2018 16 2 77 93 10.1080/1539445X.2018.1424638
    [Google Scholar]
  10. Maji R. Omolo C.A. Jaglal Y. Singh S. Devnarain N. Mocktar C. Govender T. A transferosome-loaded bigel for enhanced transdermal delivery and antibacterial activity of vancomycin hydrochloride. Int. J. Pharm. 2021 607 120990 10.1016/j.ijpharm.2021.120990 34389419
    [Google Scholar]
  11. Sagiri S.S. Singh V.K. Kulanthaivel S. Banerjee I. Basak P. Battachrya M.K. Pal K. Stearate organogel–gelatin hydrogel based bigels: Physicochemical, thermal, mechanical characterizations and in vitro drug delivery applications. J. Mech. Behav. Biomed. Mater. 2015 43 1 17 10.1016/j.jmbbm.2014.11.026 25549573
    [Google Scholar]
  12. Satapathy S. Singh V.K. Sagiri S.S. Agarwal T. Banerjee I. Bhattacharya M.K. Kumar N. Pal K. Development and characterization of gelatin‐based hydrogels, emulsion hydrogels, and bigels: A comparative study. J. Appl. Polym. Sci. 2015 132 8 app.41502 10.1002/app.41502
    [Google Scholar]
  13. Lupi F.R. Shakeel A. Greco V. Oliviero Rossi C. Baldino N. Gabriele D. A rheological and microstructural characterisation of bigels for cosmetic and pharmaceutical uses. Mater. Sci. Eng. C 2016 69 358 365 10.1016/j.msec.2016.06.098 27612723
    [Google Scholar]
  14. Fasolin L.H. Martins A.J. Cerqueira M.A. Vicente A.A. Modulating process parameters to change physical properties of bigels for food applications. Food Structure 2021 28 100173 10.1016/j.foostr.2020.100173
    [Google Scholar]
  15. Golodnizky D. Davidovich-Pinhas M. The effect of the HLB value of sucrose ester on physiochemical properties of bigel systems. Foods 2020 9 12 1857 10.3390/foods9121857 33322787
    [Google Scholar]
  16. Kodela S.P. Pandey P.M. Nayak S.K. Uvanesh K. Anis A. Pal K. Novel agar–stearyl alcohol oleogel-based bigels as structured delivery vehicles. Int. J. Polym. Mater. 2017 66 13 669 678 10.1080/00914037.2016.1252362
    [Google Scholar]
  17. Bollom M.A. Clark S. Acevedo N.C. Edible lecithin, stearic acid, and whey protein bigels enhance survival of probiotics during in vitro digestion. Food Biosci. 2021 39 100813 10.1016/j.fbio.2020.100813
    [Google Scholar]
  18. Guo Z. Chen Z. Meng Z. Bigels constructed from hybrid gelator systems: Bulk phase-interface stability and 3D printing. Food Funct. 2023 14 11 5078 5089 10.1039/D3FO00948C 37161523
    [Google Scholar]
  19. Wang X. Li H. Liu Y. Ding S. Jiang L. Wang R. A novel edible solid fat substitute: Preparation of biphasic stabilized bigels based on glyceryl monolaurate and gellan gum. Int. J. Biol. Macromol. 2024 263 Pt 2 130081 10.1016/j.ijbiomac.2024.130081 38423907
    [Google Scholar]
  20. Zheng H. Mao L. Cui M. Liu J. Gao Y. Development of food-grade bigels based on κ-carrageenan hydrogel and monoglyceride oleogels as carriers for β-carotene: Roles of oleogel fraction. Food Hydrocoll. 2020 105 105855 10.1016/j.foodhyd.2020.105855
    [Google Scholar]
  21. Shakeel A. Farooq U. Gabriele D. Marangoni A.G. Lupi F.R. Bigels and multi-component organogels: An overview from rheological perspective. Food Hydrocoll. 2021 111 106190 10.1016/j.foodhyd.2020.106190
    [Google Scholar]
  22. Soni K. Gour V. Agrawal P. Haider T. Kanwar I.L. Bakshi A. Soni V. Carbopol-olive oil-based bigel drug delivery system of doxycycline hyclate for the treatment of acne. Drug Dev. Ind. Pharm. 2021 47 6 954 962 34280061
    [Google Scholar]
  23. Paul S.R. Qureshi D. Yogalakshmi Y. Nayak S.K. Singh V.K. Syed I. Sarkar P. Pal K. Development of bigels based on stearic acid–rice bran oil oleogels and tamarind gum hydrogels for controlled delivery applications. J. Surfactants Deterg. 2018 21 1 17 29 10.1002/jsde.12022
    [Google Scholar]
  24. Rehman K. Zulfakar M.H. Novel fish oil-based bigel system for controlled drug delivery and its influence on immunomodulatory activity of imiquimod against skin cancer. Pharm. Res. 2017 34 1 36 48 10.1007/s11095‑016‑2036‑8 27620176
    [Google Scholar]
  25. Valoppi F. Calligaris S. Barba L. Šegatin N. Poklar Ulrih N. Nicoli M.C. Influence of oil type on formation, structure, thermal, and physical properties of monoglyceride‐based organogel. Eur. J. Lipid Sci. Technol. 2017 119 2 1500549 10.1002/ejlt.201500549
    [Google Scholar]
  26. Singh V.K. Banerjee I. Agarwal T. Pramanik K. Bhattacharya M.K. Pal K. Guar gum and sesame oil based novel bigels for controlled drug delivery. Colloids Surf. B Biointerfaces 2014 123 582 592 10.1016/j.colsurfb.2014.09.056 25444661
    [Google Scholar]
  27. Shakeel A. Farooq U. Iqbal T. Yasin S. Lupi F.R. Gabriele D. Key characteristics and modelling of bigels systems: A review. Mater. Sci. Eng. C 2019 97 932 953 10.1016/j.msec.2018.12.075 30678982
    [Google Scholar]
  28. Rehman K. Zulfakar M.H. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev. Ind. Pharm. 2014 40 4 433 440 10.3109/03639045.2013.828219 23937582
    [Google Scholar]
  29. Roy H. Maddela S. Munagala A. Rahaman S.A. Nandi S. A quality by design approach of metronidazole bigel and assessment of antimicrobial study utilizing box-behnken design. Comb. Chem. High Throughput Screen. 2021 24 10 1628 1643 33380293
    [Google Scholar]
  30. Kouider Amar M. Rahal S. Laidi M. Kouar I. Bourahla R.F.E.K. Akouche Y. Bouaraba R. Balancing competing objectives in bigel formulations using many-objective optimization algorithms and different decision-making methods. Eur. J. Pharm. Biopharm. 2024 195 114167 10.1016/j.ejpb.2023.12.007 38122946
    [Google Scholar]
  31. Singh B. Kumar R. Designing biocompatible sterile organogel–bigel formulations for drug delivery applications using green protocol. New J. Chem. 2019 43 7 3059 3070 10.1039/C8NJ05480K
    [Google Scholar]
  32. Hamed R. AbuRezeq A. Tarawneh O. Development of hydrogels, oleogels, and bigels as local drug delivery systems for periodontitis. Drug Dev. Ind. Pharm. 2018 44 9 1488 1497 10.1080/03639045.2018.1464021 29669437
    [Google Scholar]
  33. Wróblewska M. Szymańska E. Szekalska M. Winnicka K. Different types of gel carriers as metronidazole delivery systems to the oral mucosa. Polymers 2020 12 3 680 32204334
    [Google Scholar]
  34. Samui T. Goldenisky D. Rosen-Kligvasser J. Davidovich-Pinhas M. The development and characterization of novel in-situ bigel formulation. Food Hydrocoll. 2021 113 106416 10.1016/j.foodhyd.2020.106416
    [Google Scholar]
  35. Charyulu R.N. Muaralidharan A. Sandeep D.S. Design and evaluation of bigels containing flurbiprofen. Res J Pharm Technol 2018 11 1 143 152 10.5958/0974‑360X.2018.00028.8
    [Google Scholar]
  36. Kasparaviciene G. Maslii Y. Herbina N. Kazlauskiene D. Marksa M. Bernatoniene J. Development and evaluation of two-phase gel formulations for enhanced delivery of active ingredients: Sodium diclofenac and camphor. Pharmaceutics 2024 16 3 366 10.3390/pharmaceutics16030366 38543261
    [Google Scholar]
  37. Andonova V.Y. Peneva P.T. Apostolova E.G. Dimcheva T.D. Peychev Z.L. Kassarova M.I. Carbopol hydrogel/sorbitan monostearate-almond oil based organogel biphasic formulations: Preparation and characterization of the bigels. Trop. J. Pharm. Res. 2017 16 7 1455 1463
    [Google Scholar]
  38. Rehman K. Mohd Amin M.C.I. Zulfakar M.H. Development and physical characterization of polymer-fish oil bigel (hydrogel/oleogel) system as a transdermal drug delivery vehicle. J. Oleo Sci. 2014 63 10 961 970 10.5650/jos.ess14101 25252741
    [Google Scholar]
  39. Hashemi B. Assadpour E. Jafari S.M. Bigels as novel carriers of bioactive compounds: Applications and research trends. Food Hydrocoll. 2024 147 109427 10.1016/j.foodhyd.2023.109427
    [Google Scholar]
  40. Lupi F.R. De Santo M.P. Ciuchi F. Baldino N. Gabriele D. A rheological modelling and microscopic analysis of bigels. Rheol. Acta 2017 56 9 753 763 10.1007/s00397‑017‑1030‑3
    [Google Scholar]
  41. Mukherjee S Majee SB Biswas GR Formulation and in vitro characterisation of soybean oil-HPMCK4M based bigel matrix for topical drug delivery. Int. J. Appl. Pharm. 2019 33 38
    [Google Scholar]
  42. Behera B. Sagiri S.S. Singh V.K. Pal K. Anis A. Mechanical properties and delivery of drug/probiotics from starch and non‐starch based novel bigels: A comparative study. Stärke 2014 66 9-10 865 879 10.1002/star.201400045
    [Google Scholar]
  43. Almeida I.F. Fernandes A.R. Fernandes L. Pena Ferreira M.R. Costa P.C. Bahia M.F. Moisturizing effect of oleogel/hydrogel mixtures. Pharm. Dev. Technol. 2008 13 6 487 494 10.1080/10837450802282447 18720247
    [Google Scholar]
  44. Martins A.J. Silva P. Maciel F. Pastrana L.M. Cunha R.L. Cerqueira M.A. Vicente A.A. Hybrid gels: Influence of oleogel/hydrogel ratio on rheological and textural properties. Food Res. Int. 2019 116 1298 1305 10.1016/j.foodres.2018.10.019 30716919
    [Google Scholar]
  45. Ibrahim MM Hafez SA Mahdy MM Organogels, hydrogels and bigels as transdermal delivery systems for diltiazem hydrochloride. Asian J. Pharm. Sci. 2013 8 1 48 57
    [Google Scholar]
  46. Lupi F.R. Gentile L. Gabriele D. Mazzulla S. Baldino N. de Cindio B. Olive oil and hyperthermal water bigels for cosmetic uses. J. Colloid Interface Sci. 2015 459 70 78 10.1016/j.jcis.2015.08.013 26263497
    [Google Scholar]
  47. Rehman K. Aluwi M.F.F.M. Rullah K. Wai L.K. Mohd Amin M.C.I. Zulfakar M.H. Probing the effects of fish oil on the delivery and inflammation-inducing potential of imiquimod. Int. J. Pharm. 2015 490 1-2 131 141 10.1016/j.ijpharm.2015.05.045 26003416
    [Google Scholar]
  48. Chao E. Li J. Duan Z. Fan L. Bigels as emerging biphasic systems: Properties, applications, and prospects in the food industry. Food Hydrocoll. 2024 154 110089 10.1016/j.foodhyd.2024.110089
    [Google Scholar]
  49. Pehlivanoğlu H. Demirci M. Toker O.S. Konar N. Karasu S. Sagdic O. Oleogels, a promising structured oil for decreasing saturated fatty acid concentrations: Production and food-based applications. Crit. Rev. Food Sci. Nutr. 2018 58 8 1330 1341 10.1080/10408398.2016.1256866 27830932
    [Google Scholar]
  50. Bascuas S. Morell P. Hernando I. Quiles A. Recent trends in oil structuring using hydrocolloids. Food Hydrocoll. 2021 118 106612 10.1016/j.foodhyd.2021.106612
    [Google Scholar]
  51. Martins A.J. Vicente A.A. Cunha R.L. Cerqueira M.A. Edible oleogels: An opportunity for fat replacement in foods. Food Funct. 2018 9 2 758 773 10.1039/C7FO01641G 29417124
    [Google Scholar]
  52. Kim J. Kim D.N. Lee S.H. Yoo S.H. Lee S. Correlation of fatty acid composition of vegetable oils with rheological behaviour and oil uptake. Food Chem. 2010 118 2 398 402 10.1016/j.foodchem.2009.05.011
    [Google Scholar]
  53. Orsavova J. Misurcova L. Ambrozova J. Vicha R. Mlcek J. Fatty acids composition of vegetable oils and its contribution to dietary energy intake and dependence of cardiovascular mortality on dietary intake of fatty acids. Int. J. Mol. Sci. 2015 16 6 12871 12890 10.3390/ijms160612871 26057750
    [Google Scholar]
  54. Gonçalves R.F.S. Zhou H. Vicente A.A. Pinheiro A.C. McClements D.J. Plant-based bigels for delivery of bioactive compounds: Influence of hydrogel:oleogel ratio and protein concentration on their physicochemical properties. Food Hydrocoll. 2024 150 109721 10.1016/j.foodhyd.2023.109721
    [Google Scholar]
  55. Zampouni K. Sideris N. Tsavdaris E. Katsanidis E. On the structural and mechanical properties of mixed coconut and olive oil oleogels and bigels. Int. J. Biol. Macromol. 2024 268 Pt 2 131942 10.1016/j.ijbiomac.2024.131942 38685546
    [Google Scholar]
  56. Raeisi A. Farjadian F. Commercial hydrogel product for drug delivery based on route of administration. Front Chem. 2024 12 1336717 10.3389/fchem.2024.1336717 38476651
    [Google Scholar]
  57. Mao J. Meng Z. Fabrication and characterization of novel high internal phase bigels with high mechanical properties: Phase inversion and personalized edible 3D food printing. Food Hydrocoll. 2024 153 110019 10.1016/j.foodhyd.2024.110019
    [Google Scholar]
  58. Behera B. Dey S. Sharma V. Pal K. Rheological and viscoelastic properties of novel sunflower oil‐span 40‐biopolymer–based bigels and their role as a functional material in the delivery of antimicrobial agents. Adv. Polym. Technol. 2015 34 2 adv.21488 10.1002/adv.21488
    [Google Scholar]
  59. Sahoo S. Singh V.K. Uvanesh K. Biswal D. Anis A. Rana U.A. Al-Zahrani S.M. Pal K. Development of ionic and non‐ionic natural gum‐based bigels: Prospects for drug delivery application. J. Appl. Polym. Sci. 2015 132 38 app.42561 10.1002/app.42561
    [Google Scholar]
  60. Mazurkeviciute A. Ramanauskiene K. Ivaskiene M. Grigonis A. Briedis V. Topical antifungal bigels: Formulation, characterization and evaluation. Acta Pharm. 2018 68 2 223 233 10.2478/acph‑2018‑0014 29702483
    [Google Scholar]
  61. Andonova V. Peneva P. Georgiev G.S. Toncheva V.T. Apostolova E. Peychev Z. Dimitrova S. Katsarova M. Petrova N. Kassarova M. Ketoprofen-loaded polymer carriers in bigel formulation: An approach to enhancing drug photostability in topical application forms. Int. J. Nanomedicine 2017 12 6221 6238 10.2147/IJN.S140934 28894363
    [Google Scholar]
  62. Martín-Illana A. Cazorla-Luna R. Notario-Pérez F. Bedoya L.M. Ruiz-Caro R. Veiga M.D. Freeze-dried bioadhesive vaginal bigels for controlled release of Tenofovir. Eur. J. Pharm. Sci. 2019 127 38 51 10.1016/j.ejps.2018.10.013 30343152
    [Google Scholar]
  63. Hamed R. Mahmoud N.N. Alnadi S.H. Alkilani A.Z. Hussein G. Diclofenac diethylamine nanosystems-loaded bigels for topical delivery: Development, rheological characterization, and release studies. Drug Dev. Ind. Pharm. 2020 46 10 1705 1715 10.1080/03639045.2020.1820038 32892653
    [Google Scholar]
  64. Wakhet S. Singh V.K. Sahoo S. Sagiri S.S. Kulanthaivel S. Bhattacharya M.K. Kumar N. Banerjee I. Pal K. Characterization of gelatin–agar based phase separated hydrogel, emulgel and bigel: A comparative study. J. Mater. Sci. Mater. Med. 2015 26 2 118 10.1007/s10856‑015‑5434‑2 25672596
    [Google Scholar]
/content/journals/crcep/10.2174/0127724328288796240906040927
Loading
/content/journals/crcep/10.2174/0127724328288796240906040927
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: drug delivery ; systematic review ; hydrogel ; Bigel ; organogel
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test