Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies

Sedat ÜNAL, (Erciyes Üniversitesi, Eczacılık Fakültesi, Farmasötik Teknoloji Anabilim Dalı, Kayseri, Türkiye)
Kerem polat, (Erzincan Binali Yıldırım Üniversitesi, Eczacılık Fakültesi, Farmasötik Teknoloji Anabilim Dalı, Erzincan, Türkiye.)
Dönay YUVALI, (Erciyes Üniversitesi, Eczacılık Fakültesi, Analitik Kimya Anabilim Dalı, Kayseri, Türkiye)
Esra KÖNGÜL ŞAFAK (Erciyes Üniversitesi, Eczacılık Fakültesi, Farmakognozi Anabilim Dalı, Kayseri, Türkiye)
Journal of research in pharmacy (online)
1 0
Yıl: 2023 Cilt: 27 Sayı: 1 Sayfa Aralığı: 97 - 119 Metin Dili: İngilizce DOI: 10.29228/jrp.296 İndeks Tarihi: 30-05-2023

Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies

Öz:
In this study, cyclodextrin (HP-β-CD) inclusion complexes were prepared with Curcumin (CUR) by cosolvency/lyophilization method. Characterization studies were performed with phase-solubility diagrams, scanning electron microscopy (SEM), FT-IR, FT-Raman, XRD, Differential scanning calorimetry (DSC). The prepared CUR:HP-β-CD complexes were evaluated for their anti-oxidant and anti-inflammatory activities compared to free CUR and significantly higher activity was detected with the complexation. In addition, pre-formulation studies have been completed in order to develop an in situ gel formulation, containing CUR:HP-β-CD, suitable for use in ocular diseases. To prepare the in situ forming gels, different Pluronic F127 (PF127) concentrations were used. Chitosan was added to the formulations to improve the gel's mucoadhesive properties. The formulations were evaluated for their viscosity pH, clarity, and sol-gel transition temperature. It was established that the formulations were all clear, their pH was 6, their gelation temperature decreased with increasing PF127, and was between 26-35 °C. Viscosities of all formulations were found to be suitable for ocular application. For the selected formulation, CUR and CUR:HP-β-CD were loaded to in situ gelling systems. In vitro release experiments revealed that the CUR:HP-CD inclusion complex including NSL formulation released for 6 hours with a higher burst effect than the other formulation. At the end of the study, in situ gel formulations containing CUR:HP-β-CD were successfully prepared and characterized comprehensively. In addition, a detailed release kinetic study was conducted for the formulations and it was determined that the CUR release from the in situ gel formulations was compatible with the Weibull model. In conclusion, a mucoadhesive in situ gel formulation containing anti-oxidant and anti-inflammatory CUR:HP-β-CD complex for ocular diseases is presented as an innovative formulation approach.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • [1] Guo C, Cui F, Li M, Li F, Wu X. Enhanced corneal permeation of coumarin-6 using nanoliposomes containing dipotassium glycyrrhizinate: in vitro mechanism and in vivo permeation evaluation. RSC Advances. 2015;5(92):75636-47. [CrossRef]
  • [2] Bucolo C, Drago F, Salomone S. Ocular drug delivery: a clue from nanotechnology. Frontiers Media SA; 2012. p. 188. [CrossRef]
  • [3] Joseph RR, Venkatraman SS. Drug delivery to the eye: what benefits do nanocarriers offer? Nanomedicine. 2017;12(6):683-702. [CrossRef]
  • [4] Vaishya RD, Khurana V, Patel S, Mitra AK. Controlled ocular drug delivery with nanomicelles. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2014;6(5):422-37. [CrossRef]
  • [5] Srividya B, Cardoza RM, Amin P. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. Journal of controlled release. 2001;73(2-3):205-11. [CrossRef]
  • [6] Liu Z, Li J, Nie S, Liu H, Ding P, Pan W. Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. International journal of pharmaceutics. 2006;315(1-2):12-7. [CrossRef]
  • [7] Wei G, Xu H, Ding PT, Zheng JM. Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies. Journal of Controlled Release. 2002;83(1):65-74. [CrossRef]
  • [8] Almeida H, Amaral MH, Lobão P, Lobo JMS. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug discovery today. 2014;19(4):400-12. [CrossRef]
  • [9] Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharmaceutical research. 2006;23(12):2709-28. [CrossRef]
  • [10] Muxika A, Etxabide A, Uranga J, Guerrero P, De La Caba K. Chitosan as a bioactive polymer: Processing, properties and applications. International Journal of Biological Macromolecules. 2017;105:1358-68. [CrossRef]
  • [11] Fazel Nabavi S, Thiagarajan R, Rastrelli L, Daglia M, Sobarzo-Sanchez E, Alinezhad H, Nabavi SM. Curcumin: a natural product for diabetes and its complications. Current topics in medicinal chemistry. 2015;15(23):2445-55. [CrossRef]
  • [12] Lou J, Hu W, Tian R, Zhang H, Jia Y, Zhang J, Zhang L. Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles. International journal of nanomedicine. 2014;9:2517. [CrossRef]
  • [13] Xie P, Zhang W, Yuan S, Chen Z, Yang Q, Yuan D, Wang F, Liu QH. Suppression of experimental choroidal neovascularization by curcumin in mice. PloS one. 2012;7(12):e53329. [CrossRef]
  • [14] Pradhan N, Guha R, Chowdhury S, Nandi S, Konar A, Hazra S. Curcumin nanoparticles inhibit corneal neovascularization. Journal of Molecular Medicine. 2015;93(10):1095-106. [CrossRef]
  • [15] Pescosolido N, Giannotti R, Plateroti AM, Pascarella A, Nebbioso M. Curcumin: therapeutical potential in ophthalmology. Planta medica. 2014;80(04):249-54. [CrossRef]
  • [16] Ma X, Zhao Y. Biomedical applications of supramolecular systems based on host–guest interactions. Chemical reviews. 2015;115(15):7794-839. [CrossRef]
  • [17] Trapani A, Lopedota A, Franco M, Cioffi N, Ieva E, Garcia-Fuentes M, Alonso MJ. A comparative study of chitosan and chitosan/cyclodextrin nanoparticles as potential carriers for the oral delivery of small peptides. European Journal of Pharmaceutics and Biopharmaceutics. 2010;75(1):26-32. [CrossRef]
  • [18] Qiu N, Li X, Liu J. Application of cyclodextrins in cancer treatment. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2017;89(3-4):229-46. [CrossRef]
  • [19] Polat HK, Pehlivan SB, Özkul C, Çalamak S, Öztürk N, Aytekin E, Fırat A, Ulubayram K, Kocabeyoglu S, İrkeç M, Çalış S. Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation. International journal of pharmaceutics. 2020;585:119552. [CrossRef]
  • [20] Zuorro A, Fidaleo M, Lavecchia R. Solubility Enhancement and Antibacterial Activity of Chloramphenicol Includedin Modified β-Cyclodextrins. Bulletin of the Korean Chemical Society. 2010;31(11):3460-2. [CrossRef]
  • [21] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. Journal of pharmacy and pharmacology. 2010;62(11):1607-21. [CrossRef]
  • [22] Rodriguez-Aller M, Guinchard S, Guillarme D, Pupier M, Jeannerat D, Rivara-Minten E, Veuthey JL, Gurny R. New prostaglandin analog formulation for glaucoma treatment containing cyclodextrins for improved stability, solubility and ocular tolerance. European Journal of Pharmaceutics and Biopharmaceutics. 2015;95:203-14. [CrossRef]
  • [23] Nabih Maria D, Mishra SR, Wang L, Abd-Elgawad A-EH, Soliman OA-E, El-Dahan MS, Jablonski MM. Water-soluble complex of curcumin with cyclodextrins: enhanced physical properties for ocular drug delivery. Current Drug Delivery. 2017;14(6):875-86. [CrossRef]
  • [24] Mangolim CS, Moriwaki C, Nogueira AC, Sato F, Baesso ML, Neto AM, Matioli G. Curcumin–β-cyclodextrin inclusion complex: Stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food chemistry. 2014;153:361-70. [CrossRef]
  • [25] Chen J, Qin X, Zhong S, Chen S, Su W, Liu Y. Characterization of curcumin/cyclodextrin polymer inclusion complex and investigation on its antioxidant and antiproliferative activities. Molecules. 2018;23(5):1179. [CrossRef]
  • [26] Rojas-Mena AR, López-González H, Rojas-Hernández A. Preparation and characterization of holmium-beta-cyclodextrin complex. Advances in Materials Physics and Chemistry. 2015;5(03):87. [CrossRef]
  • [27] Van Nong H, Hung LX, Thang PN, Chinh VD, Vu LV, Dung PT, Van Trung T, Nga PT. Fabrication and vibration characterization of curcumin extracted from turmeric (Curcuma longa) rhizomes of the northern Vietnam. SpringerPlus. 2016;5(1):1-9. [CrossRef]
  • [28] Denadai AM, Santoro MM, Lopes MT, Chenna A, de Sousa FB, Avelar GM, Gomes MRT, Guzman F, Salas CE, Sinisterra RD. A supramolecular complex between proteinases and β-cyclodextrin that preserves enzymatic activity. Biodrugs. 2006;20(5):283-91. [CrossRef]
  • [29] Mashaqbeh H, Obaidat R, Al-Shar’i N. Evaluation and Characterization of Curcumin-β-Cyclodextrin and Cyclodextrin-Based Nanosponge Inclusion Complexation. Polymers. 2021;13(23):4073. [CrossRef]
  • [30] Gaudana R, Jwala J, Boddu SH, Mitra AK. Recent perspectives in ocular drug delivery. Pharmaceutical research. 2009;26(5):1197-216. [CrossRef]
  • [31] Lumry WR. A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis. Journal of allergy and clinical immunology. 1999;104(4):s150-s9. [CrossRef]
  • [32] Singh R, Tønnesen HH, Vogensen SB, Loftsson T, Másson M. Studies of curcumin and curcuminoids. XXXVI. The stoichiometry and complexation constants of cyclodextrin complexes as determined by the phase-solubility method and UV–Vis titration. Journal of inclusion phenomena and macrocyclic chemistry. 2010;66(3):335-48. [CrossRef]
  • [33] Pramanik A, Sahoo RN, Nanda A, Mohapatra R, Singh R, Mallick S. Ocular permeation and sustained anti-inflammatory activity of dexamethasone from kaolin nanodispersion hydrogel system. Current Eye Research. 2018;43(6):828-38. [CrossRef]
  • [34] Bohorquez M, Koch C, Trygstad T, Pandit N. A study of the temperature-dependent micellization of pluronic F127. Journal of colloid and interface science. 1999;216(1):34-40. [CrossRef]
  • [35] Okur NÜ, Yozgatli V, Okur ME. In vitro–in vivo evaluation of tetrahydrozoline loaded ocular in situ gels on rabbits for allergic conjunctivitis management. Drug Development Research. 2020;81(6):716-27. [CrossRef]
  • [36] Çulcu Ö, Tunçel E, TAMER Sİ, TIRNAKSIZ FF. Characterization of Thermosensitive Gels for the Sustained Delivery of Dexketoprofen Trometamol for Dermal Applications. Journal of Gazi University Health Sciences Institute. 2020;2(2):1-12.
  • [37] Aderibigbe BA. In situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics. 2018;10(2):40. [CrossRef]
  • [38] Destruel P-L, Zeng N, Brignole-Baudouin F, Douat S, Seguin J, Olivier E, Dutot M, Rat P, Dufay S, Dufay-Wojcicki A, Maury M, Mignet N, Boudy V. In situ gelling ophthalmic drug delivery system for the optimization of diagnostic and preoperative mydriasis: in vitro drug release, cytotoxicity and mydriasis pharmacodynamics. Pharmaceutics. 2020;12(4):360. [CrossRef]
  • [39] Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie S. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263-71. [CrossRef]
  • [40] Virto MR, Elorza B, Torrado S, Elorza MdLA, Frutos G. Improvement of gentamicin poly (D, L-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures. Biomaterials. 2007;28(5):877-85. [CrossRef]
  • [41] Li N, Wang N, Wu T, Qiu C, Wang X, Jiang S, Zhang Z, Liu T, Wei C, Wang T. Preparation of curcumin-hydroxypropyl-β-cyclodextrin inclusion complex by cosolvency-lyophilization procedure to enhance oral bioavailability of the drug. Drug Development and Industrial Pharmacy. 2018;44(12):1966-74. [CrossRef]
  • [42] Higuchi T. A phase solubility technique. Adv Anal Chem Instrum. 1965;4:117-211.
  • [43] Loftsson T, Hreinsdóttir D, Másson M. Evaluation of cyclodextrin solubilization of drugs. International journal of pharmaceutics. 2005;302(1-2):18-28. [CrossRef]
  • [44] Waslidge NB, Hayes DJ. A colorimetric method for the determination of lipoxygenase activity suitable for use in a high throughput assay format. Analytical biochemistry. 1995;231(2):354-8. [CrossRef]
  • [45] Chung LY, Soo WK, Chan KY, Mustafa MR, Goh SH, Imiyabir Z. Lipoxygenase inhibiting activity of some Malaysian plants. Pharmaceutical Biology. 2009;47(12):1142-8. [CrossRef]
  • [46] Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free radical biology and medicine. 1999;26(9-10):1231-7. [CrossRef]
  • [47] El-Kamel A. In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International journal of pharmaceutics. 2002;241(1):47-55. [CrossRef]
  • [48] Gupta H, Jain S, Mathur R, Mishra P, Mishra AK, Velpandian T. Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system. Drug delivery. 2007;14(8):507-15. [CrossRef]
  • [49] Karatas A, Sonakin O, Kilicarslan M, Baykara T. Poly (ε-caprolactone) microparticles containing levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: Effects of some formulation parameters on microparticle characteristics. Journal of microencapsulation. 2009;26(1):63-74. [CrossRef]
  • [50] Gamal A, Saeed H, El-Ela FIA, Salem HF. Improving the antitumor activity and bioavailability of sonidegib for the treatment of skin cancer. Pharmaceutics. 2021;13(10):1560. [CrossRef]
  • [51] Murtaza G, Ahmad M, Khan SA, Hussain I. Evaluation of cefixime-loaded chitosan microspheres: Analysis of dissolution data using DDSolver. Dissolution Technologies. 2012;19(2):13-9. [CrossRef]
  • [52] FDA U. Guidance for Industry: Dissolution testing of immediate-release solid oral dosage forms. Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 1997:1-11.
  • [53] Aldeek F, McCutcheon N, Smith C, Miller JH, Danielson TL. Dissolution Testing of Nicotine Release from OTDN Pouches: Product Characterization and Product-to-Product Comparison. Separations. 2021;8(1):7. [CrossRef]
  • [54] Puthli S, Vavia PR. Stability studies of microparticulate system with piroxicam as model drug. Aaps Pharmscitech. 2009;10(3):872-80. [CrossRef]
APA UNAL S, Polat H, Yuvalı D, KÖNGÜL ŞAFAK E (2023). Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. , 97 - 119. 10.29228/jrp.296
Chicago UNAL SEDAT,Polat Heybet Kerem,Yuvalı Dönay,KÖNGÜL ŞAFAK ESRA Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. (2023): 97 - 119. 10.29228/jrp.296
MLA UNAL SEDAT,Polat Heybet Kerem,Yuvalı Dönay,KÖNGÜL ŞAFAK ESRA Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. , 2023, ss.97 - 119. 10.29228/jrp.296
AMA UNAL S,Polat H,Yuvalı D,KÖNGÜL ŞAFAK E Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. . 2023; 97 - 119. 10.29228/jrp.296
Vancouver UNAL S,Polat H,Yuvalı D,KÖNGÜL ŞAFAK E Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. . 2023; 97 - 119. 10.29228/jrp.296
IEEE UNAL S,Polat H,Yuvalı D,KÖNGÜL ŞAFAK E "Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies." , ss.97 - 119, 2023. 10.29228/jrp.296
ISNAD UNAL, SEDAT vd. "Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies". (2023), 97-119. https://doi.org/10.29228/jrp.296
APA UNAL S, Polat H, Yuvalı D, KÖNGÜL ŞAFAK E (2023). Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. Journal of research in pharmacy (online), 27(1), 97 - 119. 10.29228/jrp.296
Chicago UNAL SEDAT,Polat Heybet Kerem,Yuvalı Dönay,KÖNGÜL ŞAFAK ESRA Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. Journal of research in pharmacy (online) 27, no.1 (2023): 97 - 119. 10.29228/jrp.296
MLA UNAL SEDAT,Polat Heybet Kerem,Yuvalı Dönay,KÖNGÜL ŞAFAK ESRA Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. Journal of research in pharmacy (online), vol.27, no.1, 2023, ss.97 - 119. 10.29228/jrp.296
AMA UNAL S,Polat H,Yuvalı D,KÖNGÜL ŞAFAK E Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. Journal of research in pharmacy (online). 2023; 27(1): 97 - 119. 10.29228/jrp.296
Vancouver UNAL S,Polat H,Yuvalı D,KÖNGÜL ŞAFAK E Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies. Journal of research in pharmacy (online). 2023; 27(1): 97 - 119. 10.29228/jrp.296
IEEE UNAL S,Polat H,Yuvalı D,KÖNGÜL ŞAFAK E "Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies." Journal of research in pharmacy (online), 27, ss.97 - 119, 2023. 10.29228/jrp.296
ISNAD UNAL, SEDAT vd. "Development of in situ gel containing CUR:HP-β-CD inclusion complex prepared for ocular diseases: Formulation, characterization, anti-inflammatory, anti-oxidant evaluation and comprehensive release kinetic studies". Journal of research in pharmacy (online) 27/1 (2023), 97-119. https://doi.org/10.29228/jrp.296
Sayfa Oluşturulma Tarihi
24-04-2024 7:36

İLETİŞİM

TÜBİTAK ULAKBİM TR Dizin

Yüzüncüyıl, İşçi Blokları Mahallesi

Muhsin Yazıcıoğlu Caddesi No:51/C

06530 Çankaya / ANKARA +90 (312) 298 92 00

trdizin@tubitak.gov.tr

TÜBİTAK ULAKBİM Ulusal Akademik Ağ ve Bilgi Merkezi Cahit Arf Bilgi Merkezi © Tüm Hakları Saklıdır. Gizlilik Politikası Kullanım Şartları