Büşra KARABULUT, Oya KERİMOĞLU, Timuçin UĞURLU

6816

Dendrimerler- ilaç taşıyıcı sistemler

Dendrimerler, bir çekirdek, çekirdek etrafındaki dallanma birimleri ve fonksiyonel grup olarak da adlandırılan yüzey gruplarından oluşan polimerik ilaç taşıyıcı sistemlerdir. Dendrimerlerin çeşitliliği fonksiyonel gruplarla sağlanmaktadır. Dallanma birimleri ise, dendrimerlerin tekrarlı şekilde büyümesini sağlamaktadır. Dendrimerlerin iç kısmında bulunan boşluğa etkin maddenin enkapsülasyonu mümkündür. Bu sayede, etkin maddenin kontrollü salımı sağlanabilir. Bununla birlikte, çok dallanmış yapıda bulunması ve yüzeyinde bulunan birçok fonksiyonel grup, etkin maddelerin ve çeşitli moleküllerin aynı anda konjugasyon ile dendrimere eklenmesini sağlar. Böylece etkin maddelerin spesifik bir bölgeye hedeflendirilmesi sağlanabilir, etkin maddelerin çözünürlüğü, biyoyararlanımı artırılabilir. Bu derlemede, dendrimerlerin özellikleri ve uygulama alanları değerlendirilmiştir.
Anahtar Kelimeler:

Dendrimer, ilaç taşıyıcı sistemler, hedeflendirme

Dendrimers-drug delivery systems

Dendrimers consisting a core, branching units around the core and surface groups also named as functional group are new polymeric drug delivery systems. The variety of dendrimers are provided with functional groups. Branching units of the dendrimer provide its growth iteratively. The space in the interior of the dendrimers allows encapsulation of the active ingredient possible. In this way, the controlled release of the active ingredient can be achieved. However, being in a very branched structure and having many functional groups on the surface provide the addition of variety of molecules and active ingredient by conjugation simultaneously. Thus, targeting of active ingredients to a specific site of the body can be achieved as well as the solubility and bioavailability of the active ingredients can be increased. In this paper, the properties of dendrimers and application areas were evaluated.
Keywords:

Dendrimer, drug delivery systems, targeting,

PDF

___

  • Boas U, Christensen JB, Heegaard PMH. Dendrimers: design, synthesis and chemical properties. Dendrimers in medicine and biotechnology: new molecular tools. 1st ed. Dorset; Henry Ling Ltd.; 2006. p.1-27.
  • Thompson DW. Rate of growth. In: Bonner JT, eds. Growth and Form. 6th ed. London: Cambridge University Press; 2006. p.170.
  • Tomalia DA, Frèchet JMJ. Discovery of dendrimers and dendritic polymers: a brief historical perspective. J. Polym. Sci. A.: Polymer Chemistry. 2002; 40(16): 2719–2728.
  • Buhleier E, Wehner W, Vögtle F. Cascade and nonskid-chain-like syntheses of molecular cavity topologies. Synthesis. 1978; 2: 155-158.
  • Tomalia DA, Baker H, Dewald JR, Hall M, Kallos G, Martin S, Roek J, Ryder J, Smith P. A new class of polymers: starburst- dendritic macromolecules. Polymer Journal. 1985; 17: 117-132.
  • Newkome GR, Yao Z, Baker GR, Gupta V K. Cascade molecules: a new approach to micelles. A [27]-arborol. J. Org. Chem. 1985; 50(11): 2003- 2004.
  • Bulut MO, Akar E. Dendrimerlerin önemi ve kullanım alanları. SDU Teknik Bilimler Dergisi. 2012; 2(1): 5-11.
  • Klajnert B, Bryszewska M. Dendrimers: properties and applications. Acta Biochim. Pol. 2001; 48: 199-208.
  • Hodge P. Polymer science branches out. Nature. 1993; 362: 18-19.
  • Hawker CJ, Fréchet JMJ. Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules. J. Am. Chem. Soc. 1990; 112(21): 7638-7647.
  • Zimmerman SC, Zeng F, Reichert DEC, Kolotuchin SV. Self assembling dendrimers. Science. 1996; 271: 1095-1098.
  • Mourey TH, Turner SR, Rubenstein M, Fréchet MJ, Hawker CJ, Wooley KL. Unique behaviour of dendritic macromolecules:intrinsic viscosity of polyether dendrimers. Macromolecules.1992; 25(9): 2401-2406.
  • Jansen JFGA, De Brabander Van Den Berg EMM, Meijer EW. Encapsulation of guest molecules into a dendritic box. Science, New Series. 1994; 266: 1226-1229.
  • Archut A, Azzellini GC, Balzani V, Cola LD, Vögtle F. Toward photoswitchable dendritic hosts. Interaction between azobenzene- functionalized dendrimers and eosin. J. Am. Chem. Soc. 1998; 120(47): 12187-12191.
  • Gillies ER, Fréchet JMJ. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today. 2005; 10(1): 35-43.
  • Roberts JC, Bhalgat MK, Zera RT. Preliminary biological evaluation of polyaminoamine (PAMAM) StarburstTM dendrimers. J. Biomed. Mat. Res. 1996; 30(1): 53-65.
  • Greish, TK, Giridhar, HG. Charge affects the oral toxicity of poly (amidoamine) dendrimers. Eur. J. Pharm. Biopharm. 2013; 84(2): 330- 334.
  • Caminati G, Turro NJ, Tomalia DA. Photophysical investigation of starburst dendrimers and their interactions with anionic and cationic surfactants. J. Am. Chem. Soc. 1990; 112(23): 8515-8522.
  • Fischer M, Vögtle F. Dendrimers:from design to applications -a progress report. Angew. Chem. Int. Ed. Engl. 1999; 38(7): 884-905.
  • Babu VR, Nikhat MSR, Srikanth G. Dendrimers: a new carrier system for drug delivery. International Journal of Pharmaceutical and Applied Sciences. 2010; 1: 1-10.
  • D’Emanuele A, Attwood D. Dendrimer–drug interactions. Adv. Drug Deliv. Rev. 2005; 57(15): 2147-2162.
  • Ballauff M, Likos CN. Dendrimers in solution: insight from theory and simulation. Angew. Chem. Int. Ed. Engl. 2004; 43: 2998-3020.
  • Stevelmans S, Hest JMC, Jansen JFGA, Van Boxtel DAFG, De Brabander van den Berg EMM, Meijer EW. Synthesis, characterization, and guest–host properties of inverted unimolecular dendritic micelles. J. Am. Chem. Soc.1996; 118: 7398-7399.
  • Newkome GR, Moorefield CN, Baker GR, Saunders MJ, Grossman SH. Unimolecular micelles. Angew. Chem. Int. Ed. Engl. 1991; 30(9): 1178- 1180.
  • Greenwald RB, Choe YH, McGuire J, Conover CD. Effective drug delivery by PEGylated drug conjugates. Adv. Drug Deliv. Rev. 2003;55(2):217-250.
  • Liu M, Kono K, Frèchet JMJ. Water-soluble dendritic unimolecular micelles: their potential as drug delivery agents. J. Control. Release. 2000;65(1-2):121-131.
  • Pan G, Lemmouchi Y, Akala EO, Bakare O. Studies on PEGylated and drug-loaded PAMAM dendrimers. J. Bioact. Compat. Polym.
  • Bhadra D, Bhadra S, Jain S, Jain NKA. A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int. J. Pharm. 2003; 57(1-2): 111-124.
  • Yang H, Morris JJ, Lopina, SS. Polyethylene glycol polyamidoamine dendritic micelle as solubility enhancer and the effect of the length of polyethylene glycol arms on the solubility of pyrene in water. J. Colloid Interface Sci. 2004; 273(1): 148-154.
  • Oya T, Lee J, Park K. Effects of ethylene glycol-based graft, star- shaped, and dendritic polymers on solubilization and controlled release of paclitaxel. J. Control. Release. 2003; 93: 121-127.
  • Jansen JFGA, Meijer EM, de Brabander-van den Berg, EMM. The dendritic box: shape-selective liberation of encapsulated guests. J. Am. Chem Soc. 1995; 117: 4417-4418.
  • Esfand R, Tomalia DA, Beezer AE, Mitchell JC, Hardy M, Orford C. Dendripore and dendrilock concepts new controlled delivery strategies. Polymer Preprints. 2000; 41: 1324-1325.
  • Wendland SM, Zimmerman SC. Synthesis of cored dendrimers. Journal Of American Chemistry Soceity. 1999; 121: 1389-1390.
  • Zhao Y, Zimmerman SC. Synthesis of cored dendrimers with internal cross-links. Angewandte Chemie International Edition. 2001; 40(10): 1962-1966.
  • Kim TI, Seo HJ, Choi JS, Jang HS, Baek J, Kim K, Park JS. PAMAM–PEG– PAMAM: novel triblock copolymer as a biocompatible and efficient gene delivery carrier. Biomacromolecules. 2004; 5: 2487-2492.
  • Zhu L, Zhu G, Li M, Wang E, Zhu R, Qi X. Thermosensitive aggregates self-assembled by an asymmetric block copolymer of dendritic polyether and poly(N-isopropylacrylamide). European Polymer Journal. 2002; 38(12): 2503-2506.
  • Zhang H, Dubin PL, Ray J, Manning GS, Moorefield CN, Newkome GR. Interaction of a polycation with small oppositely charged dendrimers. Journal of Physical Chemistry B. 1999; 103(13): 2347-2354.
  • Milhem OM, Myles C, McKeown NB, Attwood D, D’Emanuele A. Polyamidoamine starburst dendrimers as solubility enhancers. International Journal of Pharmaceutics. 2000; 197(1-2): 239-241.
  • Chauhan AS, Sridevi S, Chalasani KB, Jain AK, Jain SK, Jain NK, Diwan, PW. Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin. Journal of Control Release. 2003; 90(3): 335-343.
  • Yang H, Lopina ST. Extended release of a novel antidepressant, venlafaxine, based on anionic polyamidoamine dendrimers and poly(ethyleneglycol)-containing semi-interpenetrating networks. Journal Of Biomedical Material Research. 2005; 72(1): 107-114.
  • D’Emanuele A, Jevprasesphant R, Penny J, Attwood D. The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. Journal of Controlled Release. 2004; 95(3): 447-453.
  • Patri AK, Kukowska-Latallo JF, Baker JR. Targeted drug delivery with dendrimers: Comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Advanced Drug Delivery Reviews. 2005; 57(15): 2203-2214.
  • Wiener EC, Auteri FP, Chen JW, Brechbiel MW, Gansow OA, Schneider DS, Belford RL, Clarkson RB, Lauterbur PC. Moleculardynamics of ion-chelate complexes attached to dendrimers. Journal Of American Chemistry Soceity. 1996; 118(33): 7774-7782.
  • Byrant HY, Brechbiel MW, Wu C, Bulte JW, Herynek V, Frank JA. Synthesis and relaxometry of high-generation (G=5, 7, and 10) PAMAM dendrimer-DOTA-gadolinium chelates. Journal Of Magnetic Resonance Imaging. 1999; 9(2): 348-352.
  • Sadekar S, Ghandehari H. Transepithelial transport and toxicity of PAMAM endrimers: implications for oral drug delivery. Advanced Drug Delivery Reviews. 2012; 64(6): 571-588.
  • El-Sayed M, Ginski M, Rhodes C, Ghandehari H. Transepithelial transport of poly (amidoamine) dendrimers across Caco-2 cell monolayers. Journal of Controlled Release. 2002; 81: 355-365.
  • El-Sayed M, Ginski M, Rhodes CA, Ghandehari H. Influence of surfacechemistry of poly (amidoamine) dendrimers on Caco-2 cell monolayers. Journal Of Bioactive and Compatible Polymer. 2003; 18(1): 7-22.
  • El-Sayed M, Rhodes CA, Ginski M, Ghandehari H. Transport mechanism(s) of poly (amidoamine) dendrimers across Caco-2 cell monolayers. International Journal of Pharmaceutics. 2003; 265(1-2): 151-157.
  • Lin Y, Khanafer K, El-Sayed MEH. Quantitative evaluation of the effectof poly(amidoamine) dendrimers on the porosity of epithelial monolayers. Nanoscale. 2010; 2: 755-762.
  • Sadekar S, Thiagarajan G, Bartlett K, Hubbard D, Ray A. Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin. International Journal of Pharmaceutics. 2013; 456(1): 175-185.
  • Ke W, Zhao Y, Huang R, Jiang C, Pei Y. Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system. Journal of Pharmeceutical Science. 2008; 97(6): 2209-2216.
  • Sigal GB, Mammen M, Dahmann G, Whitesides GM. Polyacrylamides bearing pendant α-sialoside groups strongly inhibit agglutination of erythrocytes by influenza virus: The strong inhibition reflects enhanced binding through cooperative polyvalent interactions. American Chemical Soceity. 1996; 118(16): 3789-3800.
  • Hawthorne, MF. The role of chemistry in the development of boron neutron capture therapy of cancer. Angewandte Chemie International Edition. 1993; 32(7): 950-984.
  • Wanga Y, Guo R, Cao U, Shenb M, Shi X. Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine) dendrimers for targeted cancer therapy. Biomaterials. 2011; 32(12): 3322-3329.
  • Mignani S, Kazzouli SE, Bousmina M, Majoral JP. Dendrimer space concept for innovative nanomedicine: a futuristic vision for medicinal chemistry. Progress In Polymer Science. 2013; 38(7): 993-1008.
  • Singh P, Gupta U, Asthana A, Jain NK. Folate and Folate-PEG-PAMAM dendrimers: synthesis, characterization and targeted anticancer drug delivery potential in tumor bearing mice. Bioconjugate Chemistry. 2008; 19(11): 2239-2252.
  • Haensler J, Szoka FC. Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconjugate Chemistry.
  • Venuganti VVK, Perumal OP. Effect of poly(amidoamine) (PAMAM) dendrimer on skin permeation of 5-fluorouracil. International Journal of Pharmaceutics. 2008; 361(1-2): 230-238.
  • Mignani S, El Kazzouli S, Bousmina M, Majoral J. Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview. Advanced Drug Delivery Reviews. 2013; 65(10): 1316-1330.
  • Duan X, Sheardown H. Dendrimer crosslinked collagen as a corneal tissue engineering scaffold: mechanical properties and corneal epithelial cell interactions. Biomaterials. 2006; 27(26); 4608-4617.
  • Spataro G, Malecaze F, Turrin CO, Soler V, Duhayon C, Elena PP, Majoral JP, Caminade AM. Designing dendrimers for ocular drug delivery. European Journal of Medicinal Chemistry. 2010; 45(1): 326- 333.
Clinical and Experimental Health Sciences-Cover
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2011
  • Yayıncı: Marmara Üniversitesi
Arşiv
Sayıdaki Diğer Makaleler

İlaca bağlı dişeti hiperplazisinde takrolimusa bağlı değişimler: Olgu raporu

Neslihan NAL ACAR, Leyla KURU, Ulku NOYAN

Kanser tedavisinde yeni bir yaklaşım: Poli (ADP-riboz) polimeraz-1 inhibitörleri

Fatih TOK, Bedia KOÇYİĞİT KAYMAKÇIOĞLU

Dendrimerler- ilaç taşıyıcı sistemler

Büşra KARABULUT, Oya KERİMOĞLU, Timuçin UĞURLU

Probiyotiklerin periodontal tedavideki yeri

Hafize ÖZTÜRK ÖZENER, Bahar EREN KURU

Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler

Tijen ALKAN BOZKAYA