Journal of Literature Pharmacy Sciences

Sıcaklığa Duyarlı Lipozomların Kanser Tedavisinde Kullanımları
Uses of Thermosensitive Liposomes in Cancer Treatment
Tahir Emre YALÇINa
aGazi Üniversitesi Eczacılık Fakültesi, Farmasötik Teknoloji ABD, Ankara, TÜRKİYE
J Lit Pharm Sci. 2020;9(3):285-91
doi: 10.5336/pharmsci.2020-75806
Article Language: TR
Full Text
ÖZET
 Kanser, insanlar için en tehlikeli hastalıklardan biridir ve her yıl milyonlarca ölüme neden olmaktadır. Kanser tedavisi için cerrahi, kemoterapi, radyoterapi, immünoterapi, hormon tedavisi ve bu yöntemlerin kombinasyonlarını içeren çeşitli stratejiler geliştirilmiştir. Günümüzde nanotaşıyıcılar, kanserin tanı ve tedavisine yönelik en yeni yaklaşımlardır. Lipozomlar, miseller, polimerik nanopartiküller, nanojeller ve dendrimerler gibi nano boyuttaki ilaç taşıyıcı sistemler, kanser tedavisindeki başarıyı artırmaktadır. Bu ilaç taşıyıcı sistemler arasında kanser tedavisi için lipozomlara olan ilgi giderek artmaktadır. Kanser tedavisinde kanserli hücrelere zarar verirken sağlıklı hücrelerin etkilenmemesi çok önemlidir. Salımı uyarıcılarla tetiklenen lipozomal sistemler bu ihtiyacı karşılama potansiyeline sahiptir. Uyarıcılar, yüklenmiş ilaçların hastalıklı dokulara salınmasında önemli bir rol oynamaktadır. Işık, pH ve yüksek sıcaklık hedefe özgü uyarıcılardır. Sıcaklığa duyarlı lipozomlar, tümöre hedeflenmiş kemoterapide önemli bir araştırma alanıdır. Bölgesel vücut sıcaklığı artırımı ile sıcaklığa duyarlı lipozomların beraber kullanılması, tümör içerisindeki ilaç konsantrasyonunu artırır. Böylece ilacın antitümör etkinliği artarken yan etkiler azalır.

Anahtar Kelimeler: Lipozomlar; tedavi edici hipertermi; ilaç tedavisi
ABSTRACT
 Cancer is one of the most dangerous diseases for humans and causes millions of death every year. Various strategies including surgery, chemotherapy, radiotherapy, immunotherapy, hormone therapy, and combinations of these methods have been developed for cancer treatment. Nowadays, nanocarriers have been the latest approaches for the diagnosis and treatment of cancer. Nanoscale drug delivery systems such as liposomes, micelles, polymeric nanoparticles, nanogels, and dendrimers increase success in cancer treatment. Amongst these drug delivery systems, there has been a growing interest of liposomes for cancer treatment. It is very important for cancer treatment that healthy cells are not affected while destroying cancer cells. Trigger release liposome systems hold potential to meet this need. The triggers play a key role in releasing the encapsulated drug into the diseased tissues. The target-specific triggers are light, pH, and hyperthermia. Thermosensitive liposomes have been an important research area in the field of tumor targeted chemotherapy. The combination of increasing local body temperature and thermosensitive liposomes results in increased intratumoral drug concentrations. Thus improve the antitumor efficacy of drugs and reduce side effects.

Keywords: Liposomes; therapeutic hyperthermia; drug therapy
REFERENCES:
  1. Abdelaziz Ismael SA, Mohammed A, Hefny H. An enhanced deep learning approach for brain cancer MRI images classification using residual networks. Artif Intell Med. 2020;102.[Crossref] [PubMed] 
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.[Crossref] [PubMed] 
  3. Yalcin TE, Ilbasmis-Tamer S, Takka S. Antitumor activity of gemcitabine hydrochloride loaded lipid polymer hybrid nanoparticles (LPHNs): In vitro and in vivo. Int J Pharm. 2020;580:119246.[Crossref] [PubMed] 
  4. Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urol Oncol. 2008;26(1):57-64.[Crossref] [PubMed] 
  5. Wolinsky JB, Colson YL, Grinstaff MW. Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers. J Control Release. 2012;159(1):14-26.[Crossref] [PubMed] [PMC] 
  6. Parveen S, Sahoo SK. Polymeric nanoparticles for cancer therapy. J Drug Target. 2008;16(2):108-23.[Crossref] [PubMed] 
  7. Feng T, Wei Y, Lee RJ, Zhao L. Liposomal curcumin and its application in cancer. Int J Nanomedicine. 2017;12:6027-44.[Crossref] [PubMed] [PMC] 
  8. Yalcin TE, Ilbasmis-Tamer S, Takka S. Development and characterization of gemcitabine hydrochloride loaded lipid polymer hybrid nanoparticles (LPHNs) using central composite design. Int J Pharm. 2018;548(1):255-62.[Crossref] [PubMed] 
  9. Han HS, Choi KY, Ko H, Jeon J, Saravanakumar G, Suh YD, et al. Bioreducible core-crosslinked hyaluronic acid micelle for targeted cancer therapy. J Control Release. 2015;200:158-66.[Crossref] [PubMed] 
  10. Rodenak-Kladniew B, Islan GA, de Bravo MG, Durán N, Castro GR. Design, characterization and in vitro evaluation of linalool-loaded solid lipid nanoparticles as potent tool in cancer therapy. Colloids Surf B Biointerfaces. 2017;154:123-32.[Crossref] [PubMed] 
  11. Muddineti OS, Ghosh B, Biswas S. Current trends in using polymer coated gold nanoparticles for cancer therapy. Int J Pharm. 2015;484(1-2):252-67.[Crossref] [PubMed] 
  12. Dong X, Liu L, Zhu D, Zhang H, Leng X. Transactivator of transcription (TAT) peptide- chitosan functionalized multiwalled carbon nanotubes as a potential drug delivery vehicle for cancer therapy. Int J Nanomedicine. 2015;10:3829-40.[Crossref] [PubMed] [PMC] 
  13. Yalcin TE, Ilbasmis-Tamer S, Ibisoglu B, Özdemir A, Ark M, Takka S. Gemcitabine hydrochloride-loaded liposomes and nanoparticles: comparison of encapsulation efficiency, drug release, particle size, and cytotoxicity. Pharm Dev Technol. 2018;23(1):76-86.[Crossref] [PubMed] 
  14. Bi H, Xue J, Jiang H, Gao S, Yang D, Fang Y, et al. Current developments in drug delivery with thermosensitive liposomes. Asian J Pharm Sci. 2019;14(4):365-79.[Crossref] [PubMed] [PMC] 
  15. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761-9.[Crossref] [PubMed] 
  16. Zahednezhad F, Saadat M, Valizadeh H, Zakeri-Milani P, Baradaran B. Liposome and immune system interplay: Challenges and potentials. J Control Release. 2019;305:194-209.[Crossref] [PubMed] 
  17. Daraee H, Etemadi A, Kouhi M, Alimirzalu S, Akbarzadeh A. Application of liposomes in medicine and drug delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):381-91.[Crossref] [PubMed] 
  18. Alavi M, Karimi N, Safaei M. Application of Various Types of Liposomes in Drug Delivery Systems. Adv Pharm Bull. 2017;7(1):3-9.[Crossref] [PubMed] [PMC] 
  19. Tabandeh H, Mortazavi SA. An Investigation into Some Effective Factors on Encapsulation Efficiency of Alpha-Tocopherol in MLVs and the Release Profile from the Corresponding Liposomal Gel. Iran J Pharm Res. 2013;12(Suppl):21-30.[PubMed] [PMC] 
  20. Pashirova TN, Zhukova NA, Lukashenko SS, Valeeva FG, Burilova EA, Sapunova AS, et al. Multi-targeted approach by 2-benzimidazolylquinoxalines-loaded cationic arginine liposomes against сervical cancer cells in vitro. Colloids Surf B Biointerfaces. 2019;178:317-28.[Crossref] [PubMed] 
  21. Patil YP, Jadhav S. Novel methods for liposome preparation. Chem Phys Lipids. 2014;177:8-18.[Crossref] [PubMed] 
  22. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and Challenges of Liposome Assisted Drug Delivery. Front Pharmacol. 2015;6:286.[Crossref] [PubMed] [PMC] 
  23. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine. 2006;1(3):297-315.[PubMed] [PMC] 
  24. Bibi S, Lattmann E, Mohammed AR, Perrie Y. Trigger release liposome systems: local and remote controlled delivery? J Microencapsul. 2012;29(3):262-76.[Crossref] [PubMed] 
  25. Tagami T, Ernsting MJ, Li SD. Optimization of a novel and improved thermosensitive liposome formulated with DPPC and a Brij surfactant using a robust in vitro system. J Control Release. 2011;154(3):290-7.[Crossref] [PubMed] 
  26. Mu LM, Ju RJ, Liu R, Bu YZ, Zhang JY, Li XQ, et al. Dual-functional drug liposomes in treatment of resistant cancers. Adv Drug Deliv Rev. 2017;115:46-56.[Crossref] [PubMed] 
  27. Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics. 2017;9(2):12.[Crossref] [PubMed] [PMC] 
  28. O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, et al; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440-9.[Crossref] [PubMed] 
  29. Fassas A, Anagnostopoulos A. The use of liposomal daunorubicin (DaunoXome) in acute myeloid leukemia. Leuk Lymphoma. 2005;46(6):795-802.[Crossref] [PubMed] 
  30. Perez AT, Domenech GH, Frankel C, Vogel CL. Pegylated liposomal doxorubicin (Doxil) for metastatic breast cancer: the Cancer Research Network, Inc., experience. Cancer Invest. 2002;20 Suppl 2:22-9.[Crossref] [PubMed] 
  31. Felnerova D, Viret JF, Glück R, Moser C. Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs. Curr Opin Biotechnol. 2004;15(6):518-29.[Crossref] [PubMed] 
  32. Brosa M, García del Muro X, Mora J, Villacampa A, Pozo-Rubio T, Cubells L, et al. Orphan drugs revisited: cost-effectiveness analysis of the addition of mifamurtide to the conventional treatment of osteosarcoma. Expert Rev Pharmacoecon Outcomes Res. 2015;15(2):331-40.[Crossref] [PubMed] 
  33. Panahi Y, Farshbaf M, Mohammadhosseini M, Mirahadi M, Khalilov R, Saghfi S, et al. Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications. Artif Cells Nanomed Biotechnol. 2017;45(4):788-99.[Crossref] [PubMed] 
  34. Passero FC Jr, Grapsa D, Syrigos KN, Saif MW. The safety and efficacy of Onivyde (irinotecan liposome injection) for the treatment of metastatic pancreatic cancer following gemcitabine-based therapy. Expert Rev Anticancer Ther. 2016;16(7):697-703.[Crossref] [PubMed] 
  35. Saraf S, Jain A, Tiwari A, Verma A, Panda PK, Jain SK. Advances in liposomal drug delivery to cancer: An overview. J Drug Deliv Sci Tec. 2020;56:101549.[Crossref] 
  36. Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. Cancer Res. 2000;60(16):4440-5.[PubMed] 
  37. Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, et al. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res. 2000;60(24):6950-7.[PubMed] 
  38. Tagami T, May JP, Ernsting MJ, Li SD. A thermosensitive liposome prepared with a Cu²+ gradient demonstrates improved pharmacokinetics, drug delivery and antitumor efficacy. J Control Release. 2012;161(1):142-9.[Crossref] [PubMed] 
  39. P May J, Li S-D. Thermosensitive liposomes in cancer therapy. Recent Pat Biomed Eng. 2012;5(2):148-58.[Crossref] 
  40. de Matos MBC, Beztsinna N, Heyder C, Fens MHAM, Mastrobattista E, Schiffelers RM, et al. Thermosensitive liposomes for triggered release of cytotoxic proteins. Eur J Pharm Biopharm. 2018;132:211-21.[Crossref] [PubMed] 
  41. VanOsdol J, Ektate K, Ramasamy S, Maples D, Collins W, Malayer J, et al. Sequential HIFU heating and nanobubble encapsulation provide efficient drug penetration from stealth and temperature sensitive liposomes in colon cancer. J Control Release. 2017;247:55-63.[Crossref] [PubMed] [PMC] 
  42. Ta T, Porter TM. Thermosensitive liposomes for localized delivery and triggered release of chemotherapy. J Control Release. 2013;169(1-2):112-25.[Crossref] [PubMed] [PMC] 
  43. de Smet M, Langereis S, van den Bosch S, Grüll H. Temperature-sensitive liposomes for doxorubicin delivery under MRI guidance. J Control Release. 2010;143(1):120-7.[Crossref] [PubMed] 
  44. Chen J, He CQ, Lin AH, Gu W, Chen ZP, Li W, et al. Thermosensitive liposomes with higher phase transition temperature for targeted drug delivery to tumor. Int J Pharm. 2014;475(1-2):408-15.[Crossref] [PubMed] 
  45. Lim SK, Shin DH, Choi MH, Kim JS. Enhanced antitumor efficacy of gemcitabine-loaded temperature-sensitive liposome by hyperthermia in tumor-bearing mice. Drug Dev Ind Pharm. 2014;40(4):470-6.[Crossref] [PubMed] 
  46. Abri Aghdam M, Bagheri R, Mosafer J, Baradaran B, Hashemzaei M, Baghbanzadeh A, et al. Recent advances on thermosensitive and pH-sensitive liposomes employed in controlled release. J Control Release. 2019;315:1-22.[Crossref] [PubMed] 
  47. Anyarambhatla GR, Needham D. Enhancement of the Phase Transition Permeability of DPPC Liposomes by Incorporation of MPPC: A New Temperature-Sensitive Liposome for use with Mild Hyperthermia. J Liposome Res. 1999;9(4):491-506.[Crossref] 
  48. Landon CD, Park JY, Needham D, Dewhirst MW. Nanoscale Drug Delivery and Hyperthermia: The Materials Design and Preclinical and Clinical Testing of Low Temperature-Sensitive Liposomes Used in Combination with Mild Hyperthermia in the Treatment of Local Cancer. Open Nanomed J. 2011;3:38-64.[Crossref] [PubMed] [PMC] 
  49. Kneidl B, Peller M, Winter G, Lindner LH, Hossann M. Thermosensitive liposomal drug delivery systems: state of the art review. Int J Nanomedicine. 2014;9:4387-98.[Crossref] [PubMed] [PMC] 
  50. Ta T, Bartolak-Suki E, Park EJ, Karrobi K, McDannold NJ, Porter TM. Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating. J Control Release. 2014;194:71-81.[Crossref] [PubMed] [PMC] 
  51. Tagami T, Ernsting MJ, Li SD. Efficient tumor regression by a single and low dose treatment with a novel and enhanced formulation of thermosensitive liposomal doxorubicin. J Control Release. 2011;152(2):303-9.[Crossref] [PubMed] 
  52. Dunne M, Epp-Ducharme B, Sofias AM, Regenold M, Dubins DN, Allen C. Heat-activated drug delivery increases tumor accumulation of synergistic chemotherapies. J Control Release. 2019;308:197-208.[Crossref] [PubMed] 
  53. Sanna V, Pala N, Sechi M. Targeted therapy using nanotechnology: focus on cancer. Int J Nanomedicine. 2014;9:467-83.[Crossref] [PubMed] [PMC] 
  54. Leroux J, Roux E, Le Garrec D, Hong K, Drummond DC. N-isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles. J Control Release. 2001;72(1-3):71-84.[Crossref] [PubMed] 
  55. Han HD, Choi MS, Hwang T, Song CK, Seong H, Kim TW, et al. Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes. J Pharm Sci. 2006;95(9):1909-17.[Crossref] [PubMed] 

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-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

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Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

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Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

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