Publication: Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration
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2016-09-20
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Elsevier
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Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient`s quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly D-L(lactide-co-glycolide (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40μm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles.
Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30 days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12 months of storage under standard refrigerated conditions (41ºC), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug.
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2004/23/EC (2004). European Parliament and the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells
Albanese, A., Chan, W. C. (2011). "Effect of gold nanoparticle aggregation on cell uptake and toxicity." ACS Nano 5(7): 5478-5489.
Anand, A., Sharma, K. (2014). "Using current data to define new approach in age related macular degeneration: need to accelerate translational research." Curr Genomics 15(4): 266-277.
Andres-Guerrero, V., Zong, M., et al (2015). "Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology." J Control Release 211: 105-117.
Aubert-Pouessel, A., Bibby, D. C. (2002). "A novel in vitro delivery system for assessing the biological integrity of protein upon release from PLGA microspheres." Pharm Res 19(7): 1046-1051.
Avery, R. (2014). " Intravitreal Injection Technique And Monitoring Updated Guidelines of an Expert Panel." Retinal journal(34 sup.12).
Barcia, E., Herradon, C., Herrero-Vanrell, R (2005). "Biodegradable additives modulate ganciclovir release rate from PLGA microspheres destined to intraocular administration." Lett. Drug. Des. 2: 184-193.
Barcia, E., Herrero-Vanrell, R. (2009). "Downregulation of endotoxin-induced uveitis by intravitreal injection of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone." Exp Eye Res 89(2): 238-245.
Behar-Cohen, F. (2013). "Drug Delivery to the Vitreous Humor". Ocular Drug Delivery, Systems Barriers and Application of Nanoparticulate Systems. Florida, CRC Press.
Bertram, J. P., Rauch, M. F. (2010). "Using polymer chemistry to modulate the delivery of neurotrophic factors from degradable microspheres: delivery of BDNF." Pharm Res 27(1): 82-91.
Bolitho, C., Bayl, P. (2007). "The anti-apoptotic activity of albumin for endothelium is mediated by a partially cryptic protein domain and reduced by inhibitors of G-coupled protein and PI-3 kinase, but is independent of radical scavenging or bound lipid." J Vasc Res 44(4): 313-324.
Checa-Casalengua, P., Jiang, C. (2011). "Retinal ganglion cells survival in a glaucoma model by GDNF/Vit E PLGA microspheres prepared according to a novel microencapsulation procedure." J Control Release 156(1): 92-100.
Cho, E. R., Kang, S. W. (2005). "Poly(lactic-co-glycolic acid) microspheres as a potential bulking agent for urological injection therapy: preliminary results." J Biomed Mater Res B Appl Biomater 72(1): 166-172.
Chovatiya, R., Medzhitov, R. (2014). "Stress, inflammation, and defense of homeostasis." Mol Cell 54(2): 281-288.
Coccoli, V., Luciani, A. (2008). "Engineering of poly(epsilon-caprolactone) microcarriers to modulate protein encapsulation capability and release kinetic." J Mater Sci Mater Med 19(4): 1703-1711.
Comyn, O., Lightman, S. L. (2013). "Corticosteroid intravitreal implants vs. ranibizumab for the treatment of vitreoretinal disease." Curr Opin Ophthalmol 24(3): 248-254.
Davis, M. E. (2009). "The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic." Mol Pharm 6(3): 659-668.
Dunne, M. M., Ramtoola, Z. (2009). "Fluphenazine release from biodegradable microparticles: characterization and modelling of release." J Microencapsul 26(5): 403-410.
Engin, K. N. (2009). "Alpha-tocopherol: looking beyond an antioxidant." Mol Vis 15: 855-860.
Fernandez-Carballido, A., Puebla, P. (2006). "Radiosterilisation of indomethacin PLGA/PEGderivative microspheres: protective effects of low temperature during gamma-irradiation." Int J Pharm 313(1-2): 129-135.
Francis, G. L. (2010). "Albumin and mammalian cell culture: implications for biotechnology applications." Cytotechnology 62(1): 1-16.
Fratoddi, I. (2015). "The puzzle of toxicity of gold nanoparticles. The case-study of HeLa cells." Toxicol. Res. 4(4): 796-800.
Garbayo, E., Ansorena, E. (2008). "Sustained release of bioactive glycosylated glial cell-line derived neurotrophic factor from biodegradable polymeric microspheres." Eur J Pharm Biopharm 69(3): 844-851.
Garbayo, E., Montero-Menei, C. N. (2009). "Effective GDNF brain delivery using microspheres--a promising strategy for Parkinson's disease." J Control Release 135(2): 119-126.
Gaudana, R., et al (2010). "Ocular drug delivery." AAPS J 12(3): 348-360.
Gavini, E., Rassu, G. (2008). "Spray-dried microspheres based on methylpyrrolidinone chitosan as new carrier for nasal administration of metoclopramide." Eur J Pharm Biopharm 68(2): 245-252.
Giteau, A., Venier-Julienne, M. C. (2008). "How to achieve sustained and complete protein release from PLGA-based microparticles?" Int J Pharm 350(1-2): 14-26.
Gonciarz, A., Kus, K. (2012). "Capillary electrophoresis/frontal analysis versus equilibrium dialysis in dexamethasone sodium phosphate-serum albumin binding studies." Electrophoresis 33(22): 3323-3330.
Halliwell, B., Whiteman, M. (2004). "Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?" British Journal of Pharmacology 142(2): 231-255.
He, J. T., et al (2006). "Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres." Int J Pharm 309: 101-108.
Herrero-Vanrell, R., Bravo-Osuna, I. (2014). "The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies." Prog Retin Eye Res 42: 27-43.
Huang, X., Li, N. (2015). "Quantitative three-dimensional analysis of poly (lactic-co-glycolic acid) microsphere using hard X-ray nano-tomography revealed correlation between structural parameters and drug burst release." J Pharm Biomed Anal 112: 43-49.
Jiang, C., Moore, M. J. (2007). "Intravitreal injections of GDNF-loaded biodegradable microspheres are neuroprotective in a rat model of glaucoma." Mol Vis 13: 1783-1792.
Klose, D., Siepmann, F. (2006). "How porosity and size affect the drug release mechanisms from PLGA-based microparticles." Int J Pharm 314(2): 198-206.
Lee, B. K., Yun, Y. H. (2012). "Fabrication of drug loaded polymer microparticles with arbitrary geometries using a piezoelectric inkjet printing system." Int J Pharm 427(2): 305-310.
Madsen, C. G., Skov, A. (2015). "Simple measurements for prediction of drug release from polymer matrices - Solubility parameters and intrinsic viscosity." Eur J Pharm Biopharm 92: 1-7.
Martinez-Sancho, C., Herrero-Vanrell, R. (2003). "Poly (D,L-lactide-co-glycolide) microspheres for long-term intravitreal delivery of aciclovir: influence of fatty and non-fatty additives." J Microencapsul 20(6): 799-810.
Martinez-Sancho, C., Herrero-Vanrell, R. (2006). "Vitamin A palmitate and aciclovir biodegradable microspheres for intraocular sustained release." Int J Pharm 326(1-2): 100-106.
Miserocchi, E., Fogliato, G. (2013). "Review on the worldwide epidemiology of uveitis." Eur J Ophthalmol 23(5): 705-717.
Nita, M., Grzybowski, A. (2014). "Age-related macular degeneration in the aspect of chronic lowgrade inflammation (pathophysiological parainflammation)." Mediators Inflamm 2014: 930671.
Rafi, M., Singh, S. M. (2010). "Controlled release of bioactive recombinant human growth hormone from PLGA microparticles." J Microencapsul 27(6): 552-560.
Rodrigues, L. B., Leite, H. F. (2009). "In vitro release and characterization of chitosan films as dexamethasone carrier." Int J Pharm 368(1-2): 1-6.
Rodríguez, J., Guzmán, M. (2013).Preliminary studies on HSA microparticles to modulate dexamethasone release. CRS Chapter Congress. Valencia
Sah, H. (1999). "Stabilization of proteins against methylene chloride/water interface-induced denaturation and aggregation." J Control Release 58(2): 143-151.
Sampat, K. M., Garg, S. J. (2010). "Complications of intravitreal injections." Curr Opin Ophthalmol 21(3): 178-183.
Sapieha, P., Hamel, D. (2010). "Proliferative retinopathies: angiogenesis that blinds." Int J Biochem Cell Biol 42(1): 5-12.
Schiller, M., Franz, S. (2008). "Hypothesis: human serum borne albumin bound lipids promote cellular survival after apoptosis induction by a variety of stimuli." Apoptosis 13(2): 319-328.
Schmidt, S., Gonzalez, D. (2010). "Significance of protein binding in pharmacokinetics and pharmacodynamics." J Pharm Sci 99(3): 1107-1122.
Shah, V. P., Tsong, Y. (1998). "In vitro dissolution profile comparison--statistics and analysis of the similarity factor, f2." Pharm Res 15(6): 889-896.
Sherif, Z., Pleyer, U. (2002). "Corticosteroids in ophthalmology: past-present-future." Ophthalmologica 216(5): 305-315.
Short, B. G. (2008). "Safety evaluation of ocular drug delivery formulations: techniques and practical considerations." Toxicol Pathol 36(1): 49-62.
Srivastava, S., Kumar, R. (2015). "Modified Release Biodegradable Polymeric Microspheres of Stavudine: Cell Viability, Cellular Uptake, Hemolysis Studies and In Vivo Pharmacokinetics." Curr HIV Res 13(6): 503-516.
van Wijngaarden, P., Qureshi, S. H. (2008). "Inhibitors of vascular endothelial growth factor (VEGF) in the management of neovascular age-related macular degeneration: a review of current practice." Clin Exp Optom 91(5): 427-437.
Wang, M. (2010). "A spheres-in-sphere structure for improving protein-loading poly (lactide-coglycolide) microspheres." Polymer Degradation and Stability 95: 6-13.
Wang, Y., Gu, B. (2014). "Microspheres prepared with PLGA blends for delivery of dexamethasone for implantable medical devices." Pharm Res 31(2): 373-381.
Yao, J., Tucker, B. A. (2011). "Robust cell integration from co-transplantation of biodegradable MMP2-PLGA microspheres with retinal progenitor cells." Biomaterials 32(4): 1041-1050.
Yasukawa, T., Tabata, Y. (2011). "Recent advances in intraocular drug delivery systems." Recent Pat Drug Deliv Formul 5(1): 1-10.
Yeh, M. K., Chen, J. L. (2007). "The preparation of sustained release erythropoietin microparticle." J Microencapsul 24(1): 82-93.
Yuan, W., Wu, F. (2009). "Development of protein delivery microsphere system by a novel S/O/O/W multi-emulsion." Eur J Pharm Sci 36(2-3): 212-218.
Zhang, X., Zeng, H. (2014). "Diabetic macular edema: new concepts in patho-physiology and treatment." Cell Biosci 4: 27.