BILOSOME: A BILE SALT BASED NOVEL CARRIER SYSTEM GAINING INTEREST IN PHARMACEUTICAL RESEARCH
The human body has long provided pharmaceutical science with biomaterials of interesting applications. Bile salts (BSs) are biomaterials reminiscent of traditional surfactants with peculiar structure and self-assembled topologies. Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment i.e, low pH, the presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by the inclusion of bile salts into lipid bilayers constructs. Tremendous research in the last decade has made bilosomes a potential carrier system. Bilosomes with its name derived from bile salts (which is one of its major constituents), is a â€˜niosome-likeâ€™ colloidal carrier. Here, we focus on different aspects of bile salt based drug delivery systems including their composition, developmental techniques, characterization, comparative advantages of BS-integrated nanomedicines over conventional nanocarriers, stability, transitional modifications and scale-up â€“ emphasizing their biomedical potential in oral immunization against various diseases and delivery of peptide drugs. Bile acid-based amphiphiles, in the form of mixed micelles, bilosomes, drug conjugates and hybrid lipid-polymer nanoparticles are critically discussed as delivery systems for anticancer drugs, antimicrobial agents and therapeutic peptides/proteins, including vaccines. Current pitfalls, future perspectives, and opinions have also been outlined. Bile acid-based nanoparticles are a growing research area therefore, multifaceted pharmaceutical and biomedical applications of bile salts are to be expected in the near future.
Key words: Bile acids, bilosomes, vaccines, protein and peptides, bile salt containing liposomes, M-cell
2. Madenci D, Egelhaaf S. Self-assembly in aqueous bile salt solutions. Current Opinion in Colloid & Interface Science. 2010; 15(1-2):109â€“115.
3. Calabresi M, Andreozzi P, La Mesa C. Supramolecular association and polymorphic behaviour in systems containing bile acid salts. Molecules 2007; 12(8):1731â€“1754.
4. Natalini B, Sardella R, Gioiello A, Lanni F, Di Michele A, Marinozzi M. Determination of bile salt critical micellization concentration on the road to drug discovery. Journal of Pharmaceutical and Biomedical Analysis. 2014; 87:62â€“81.
5. Enhsen A, Kramer W, Wess G. Bile acids in drug discovery. Drug Discovery Today. 1998; 3(9):409â€“418.
6. Atanackovic M, Posa M, Heinle H, GojkoviÄ‡-Bukarica L, CvejiÄ‡ J. Solubilization of resveratrol in micellar solutions of different bile acids. Colloids and Surfaces B: Biointerfaces. 2009; 72(1):148â€“154.
7. Maestrelli F, Cirri M, Mennini N, Zerrouk N, Mura P. Improvement of oxaprozin solubility and permeability by the combined use of cyclodextrin, chitosan, and bile components. European Journal of Pharmaceutics and Biopharmaceutics. 2011; 78(3):385â€“393.
8. Selvam, S, Andrews ME, Mishra AK. A photophysical study on the role of bile salt hydrophobicity in solubilizing amphotericin B aggregates. Journal of Pharmaceutical Sciences. 2009; 98(11):4153â€“4160.
9. Elnaggar YS, El-Refaie WM, El-Massik MA, Abdallah OY. Lecithin-based nanostructured gels for skin delivery: an update on state of art and recent applications. Journal of Controlled Release. 2014; 180: 10â€“24.
10. Behl C, Pimplaskar H, Sileno A, Xia W, deMeireles J et al. Optimization of systemic nasal drug delivery with pharmaceutical excipients. Advanced Drug Delivery Reviews. 1998; 29(1â€“2):117â€“133.
11. Sanghai B., Aggarwal G., & HariKumar S. Solid self microemulsifying drug deliviry system: a review. Journal of Drug Delivery and Therapeutics, 2013; 3(3), 168-174.
12. Shin SC, Cho CW, Yang KH. Development of lidocaine gels for enhanced local anesthetic action. International Journal of Pharmaceutics. 2004; 287(1â€“2): 73â€“78.
13. Bhat S, Maitra U. Low molecular mass cationic gelators derived from deoxycholic acid: remarkable gelation of aqueous solvents. Tetrahedron. 2007; 63(31):7309â€“7320.
14. Boyd BJ. Past and future evolution in colloidal drug delivery systems. Expert Opinion on Drug Delivery. 2008; 5(1):69â€“85.
15. Kumar Malik D, Baboota S, Ahuja A, Hasan S, Ali J. Recent advances in protein and peptide drug delivery systems. Current Drug Delivery. 2007; 4(2):141â€“151.
16. Asadujjaman Md., Mishuk Ahmed Ullah, Novel approaches in lipid based drug delivery systems, Journal of Drug Delivery & Therapeutics; 2013; 3(4):124-130
17. Prajapati S., Maurya S., Das M., Tilak V., Verma K.K., Dhakar R.C., Dendrimers in drug delivery, diagnosis and therapy: basics and potential applications. Journal of Drug Delivery and Therapeutics, 2016; 6(1):67-92.
18. Dwivedi C, Sahu R, Tiwari SP, Satapathy T, Roy A, Role of liposome in novel drug delivery system, Journal of Drug Delivery and Therapeutics. 2014; 4(2):116-129
19. Demetzos C, Pippa N. Advanced drug delivery nanosystems (aDDnSs): a mini-review. Drug Delivery. 2014; 21:250â€“7.
20. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nature Reviews Drug Discovery. 2005; 4(2):145â€“60.
21. Sinico C, Fadda AM. Vesicular carriers for dermal drug delivery. Expert Opinion on Drug Delivery. 2009; 6:813â€“25.
22. Andrieux K, Forte L, Lesieur S, Patedrnostre M, Ollivon M, GrabielleMadelmont C. Solubilisation of dipalmitoyl phosphatidylcholine bilayers by sodium taurocholate: a model to study the stability of liposomes in the gastrointestinal tract and their mechanism of interaction with a model bile salt. European Journal of Pharmaceutics and Biopharmaceutics. 2009; 71(2):346â€“55.
23. Chen Y, Lu Y, Chen J, Lai J, Sun J, Hu F et al. Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. International Journal of Pharmaceutics.2009; 376(1-2):153â€“60.
24. Niu M, Tan Y, Guan P, Hovgaard L, Lu Y, Qi J et al. Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study. International Journal of Pharmaceutics. 2014; 460(1-2):119â€“30.
25. Shukla A, Mishra V, Kesharwani P. Bilosomes in the context of oral immunization: development, challenges and opportunities. Drug Discovery Today. 2016; 21(6):888-899.
26. Elnaggar Y. Multifaceted applications of bile salts in pharmacy: an emphasis on nanomedicine. International Journal of Nanomedicine. 2015; 10:3955â€“3971.
27. Gautrot JE, Zhu XX. Biodegradable polymers based on bile acids and potential biomedical applications. Journal of Biomaterials Science, Polymer Edition. 2006; 17(10):1123â€“1139.
28. Stojancevic M, Pavlovic N, Golocorbin-Kon S, Mikov M. Application of bile acids in drug formulation and delivery. Frontiers in Life Sciences. 2013; 7(3-4):112â€“22.
29. Bhattacharjee J, Verma G, Aswal V, Date A, Nagasenker M, Hasan P. Tween 80-sodium deoxycholate mixed micelles: structural characterization and application in doxorubicin delivery. The Journal of Physical Chemistry B. 2010; 114(49):16414â€“16421.
30. Garidel P, Hildebrand A, Knauf K, Blume A. Membranolytic activity of bile salts: influence of biological membrane properties and composition. Molecules 2007; 12:2292â€“326.
31. Pinto Reis C, Neufeld RJ, Ribeiro AJ, Veiga F. Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine 2006; 2:8â€“21.
32. Le DÃ©vÃ©dec F, Fuentealba D, Strandman S, Bohne C, Zhu X. Aggregation behavior of pegylated bile acid derivatives. Langmuir 2012; 28(37):13431â€“13440.
33. Le DÃ©vÃ©dec F, Strandman S, Hildgen P, Leclair G, Zhu X. PEGylated bile acids for use in drug delivery systems: enhanced solubility and bioavailability of itraconazole. Molecular Pharmaceutics. 2013; 10(8):3057â€“3066.
34. Kramer W. Transporters, Trojan horses and therapeutics: suitability of bile acid and peptide transporters for drug delivery. Biological Chemistry. 2011; 392(1-2):77â€“94.
35. Lee S, Kim K, Kumar T, Lee J, Kim S, Lee D et al. Synthesis and biological properties of insulin deoxycholic acid chemical conjugates. Bioconjugate Chemistry. 2005; 16(3):615â€“620.
36. Chen D, Wang X, Chen L, He J, Miao Z, Shen J. Novel liver-specific cholic acid-cytarabine conjugates with potent antitumor activities: synthesis and biological characterization. Acta Pharmacologica Sinica. 2011;32(5):664â€“672
37. Conacher M, Alexander J, Brewer J. Oral immunisation with peptide and protein antigens by formulation in lipid vesicles incorporating bile salts (bilosomes). Vaccine. 2001; 19(20-22):2965-2974.
38. Shukla A, Katare O, Singh B, Vyas S. M-cell targeted delivery of recombinant hepatitis B surface antigen using cholera toxin B subunit conjugated bilosomes. International Journal of Pharmaceutics. 2010; 385(1-2):47-52.
39. Shukla A, Bhatia A, Amarji B, Singh B, Katare O, Vyas S. Nano-bilosomes as potential vaccine delivery system for effective combined oral immunization against tetanus and hepatitis B. Journal of Biotechnology. 2010; 150:98â€“9.
40. Shukla A, Khatri K, Gupta P, Goyal A, Mehta A, Vyas S. Oral immunization against hepatitis B using bile salt stabilized vesicles (bilosomes). Journal of Pharmacy and Pharmaceutical Sciences. 2008; 11(1):59â€“66.
41. Shukla A, Singh B, Katare O. Significant systemic and mucosal immune response induced on oral delivery of diphtheria toxoid using nano-bilosomes. British Journal of Pharmacology. 2011; 164(2b):820-827.
42. Yang L, Tucker I, Ostergaard J. Effects of bile salts on propranolol distribution into liposomes studied by capillary electrophoresis. Journal of Pharmaceutical and Biomedical Analysis. 2011; 56(3):553â€“559.
43. Wu W, Guan P, Wu W. Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile salt. International Journal of Nanomedicine. 2011; 6:965â€“974.
44. Singh P, Prabakaran D, Jain S, Mishra V, Jaganathan K, Vyas S. Cholera toxin B subunit conjugated bile salt stabilized vesicles (bilosomes) for oral immunization. International Journal of Pharmaceutics. 2004; 278(2):379-390.
45. Mann J, Ferro V, Mullen A, Tetley L, mullen M, Carter K et al. Optimisation of a lipid based oral delivery system containing A/Panama influenza haemagglutinin. Vaccine. 2004;22(19):2425â€“2429.
46. Arora, D. Khurana B, Kumar M, Vyas S. Oral immunization against hepatitis B virus using mannosylated bilosomes. 2011; 1:45-51.
47. Mann J, Scales H, Shakir E, Alexander J, Carter K, Mullen A et al. Oral delivery of tetanus toxoid using vesicles containing bile salts (bilosomes) induces significant systemic and mucosal immunity. Methods. 2006; 38(2):90-95.
48. Montanari J, Vera M, Mensi E, Morilla M, Romero E. Nanoberries for topical delivery of antioxidants. Journal of Cosmetic Science. 2013; 64(6):469â€“481.
49. Paolino D, Cosco D, Cilurzo F, Trapasso E, Morittu V, Celia C et al. Improved in vitro and in vivo collagen biosynthesis by asiaticoside-loaded ultradeformable vesicles. Journal of Controlled Release. 2012; 162(1):143â€“151.
50. El Maghraby GM, Williams AC, Barry BW. Oestradiol skin delivery from ultradeformable liposomes: refinement of surfactant concentration. International Journal of Pharmaceutics. 2000; 196(1):63â€“74.
51. Dai Y, Zhou R, Liu L, Lu Y, Qi J, Wu W. Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation. International Journal of Nanomedicine. 2013; 8:1921â€“1933.
52. Fu Q, Fu HL, Huan L, Zhang W, Shu G, Liu M et al. Preparation of cefquinome sulfate proliposome and its pharmacokinetics in rabbit. Iranian Journal of Pharmaceutical Research. 2013; 12(4):611â€“621.
53. Velpula A, Jukanti R, Janga K, Sunkavalli S, Bandari S, Kandadi P et al. Proliposome powders for enhanced intestinal absorption and bioavailability of raloxifene hydrochloride: effect of surface charge. Drug Development and Industrial Pharmacy. 2012; 39(12):1895-1906.
54. Song K-H, Chung S-J, Shim C-K. Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes containing bile salts. Journal of Controlled Release. 2005; 106(3):298â€“308.
55. Cuna M, Alonso-Sandel M, RemuÃ±Ã¡n-LÃ³pez C, Pivel JP, Alonso-Lebrero JL, Alonso MJ. Development of phosphorylated glucomannan-coated chitosan nanoparticles as nanocarriers for protein delivery. Journal of Nanoscience and Nanotechnology. 2006; 6(9â€“10):2887â€“2895.
56. Jain S, Vyas SP. Mannosylated niosomes as adjuvant-carrier system for oral mucosal immunization. Journal of Liposome Research. 2006; 16(4): 331â€“345.
57. Jain S, Harde H, Indulkar A, Agrawal AK. Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration. Nanomedicine. 2014; 10(2):431â€“440.
58. Aburahma M. Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines. Drug Delivery. 2014:1-21.
59. Hu S, Niu M, Hu F, Lu Y, Qi J, Yin Z et al. Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media. International Journal of Pharmaceutics. 2013; 441(1-2):693-700.
60. Gebril A, Lamprou D, Alsaadi M, Stimson W, Mullen A, Ferro V. Assessment of the antigen-specific antibody response induced by mucosal administration of a GnRH conjugate entrapped in lipid nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine. 2014; 10(5):e971-e979.
61. Wilkhu J, McNeil S, Anderson D, Perrie Y. Characterization and optimization of bilosomes for oral vaccine delivery. Journal of Drug Targeting. 2013; 21(3):291-299.
62. Saettone M, Chetoni P, Cerbai R, Mazzanti G, Braghiroli L. Evaluation of ocular permeation enhancers: In vitro effects on corneal transport of four Î²-blockers, and in vitro/in vivo toxic activity. International Journal of Pharmaceutics. 1996; 142(1):103-113.
63. Brayden D, Jepson M, Baird A. Keynote review: Intestinal Peyer's patch M cells and oral vaccine targeting. Drug Discovery Today. 2005; 10(17):1145-1157.
64. Gebert, A. Rothkotter H, Pabst R. M cells in Peyerâ€™s patches of the intestine. International Review of Cytology. 1996;167:91â€“159.
65. Clark M. Exploiting M cells for drug and vaccine delivery. Advanced Drug Delivery Reviews. 2001; 50(1-2):81-106..
66. Jepson M, Clark M, Hirst B. M cell targeting by lectins: a strategy for mucosal vaccination and drug delivery. Advanced Drug Delivery Reviews. 2004; 56(4):511-525.
67. Bennett E, Mullen A, Ferro V. Translational modifications to improve vaccine efficacy in an oral influenza vaccine. Methods. 2009; 49(4):322-327.
68. Elsheikh M, Elnaggar Y, Abdallah O. Rationale employment of cell culture versus conventional techniques in pharmaceutical appraisal of nanocarriers. Journal of Controlled Release. 2014; 194:92â€“102.
69. Faustino C, Serafim C, Rijo P, Reis C. Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents. Expert Opinion on Drug Delivery, 2016; 13(8):1133-1148.
70. Chauhan M, Sahoo P, Rawat A, Singh A, Bamrara A, Sharma D. Bilosomes: A Novel Approach to Meet the Challenges in Oral Immunization. Recent Patents on Drug Delivery & Formulation. 2015; 9(3):206-217.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).