Design and development of artemisinin and dexamethasone loaded topical nanodispersion for the effective treatment of age-related macular degeneration

被引:15
作者
Ponnusamy, Chandrasekar [1 ]
Sugumaran, Abimanyu [2 ]
Krishnaswami, Venkateshwaran [1 ]
Kandasamy, Ruckmani [1 ]
Natesan, Subramanian [1 ]
机构
[1] Anna Univ, Bharathidasan Inst Technol, Dept Pharmaceut Technol, Tiruchirappalli, Tamil Nadu, India
[2] SRM Inst Sci & Technol, Dept Pharmaceut, Kattankulathur, Tamil Nadu, India
关键词
drug delivery systems; drugs; eye; blood vessels; DNA; biochemistry; nanofabrication; molecular biophysics; nanomedicine; diseases; biomedical materials; polymers; membranes; topical administration; enhanced ocular residence time; controlled prolonged drug delivery; disease site; topical ocular administration; polymeric surfactant; dexamethasone release; dexamethasone nanodispersion; AMD treatment; blood vessel formation; drug concentration; in-vitro drug release; antiangiogenic effect; artemisinin; dexamethasone loaded topical nanodispersion; age-related macular degeneration effective treatment; antivascular endothelial growth factor agents; antiangiogenic endothelial growth factor agents; antiVEGF agent; polyvinyl pyrrolidone K90; polymer concentration; Poloxamer; 407; size; 12; 0 nm to 26; 0; nm; chorioallantoic membrane assay; DNA damage; haemolysis; IN-VITRO; DELIVERY SYSTEM; DRUG-DELIVERY; PERMEABILITY; ENHANCEMENT; TRANSFERRIN; SOLUBILITY; WATER;
D O I
10.1049/iet-nbt.2019.0130
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Age-related macular degeneration (AMD) is a disease affecting the macula by the new blood vessels formation. AMD is widely treated with a combination of anti-angiogenic and anti-vascular endothelial growth factor (VEGF) agents. The topical administration of nanodispersions showed enhanced ocular residence time with controlled and prolonged drug delivery to the disease site at the back of the eye. In the present study we developed and characterized nanodispersion containing anti-angiogenic (artemisinin) and anti-VEGF agent (dexamethasone) for the topical ocular administration in order to obtain a required drug concentration in the posterior part of the eye. The nanodispersions were prepared with varying concentration of polymer, polyvinyl pyrrolidone K90 and polymeric surfactant, Poloxamer 407. The nanodispersions were found to be smooth and spherical in shape with a size range of 12-26 nm. In-vitro drug release studies showed the 90-101% of artemisinin and 55-103% of dexamethasone release from the nanodispersions. The blank formulation with a high concentration of polymer and polymeric surfactant showed an acceptable level of haemolysis and DNA damage. The chorioallantoic membrane assay suggested that the nanodispersion possess good anti-angiogenic effect. Hence the formulated artemisinin and dexamethasone nanodispersion may have the great potential for the AMD treatment.
引用
收藏
页码:868 / 874
页数:7
相关论文
共 48 条
[1]   In vitro hemolysis:: Guidance for the pharmaceutical scientist [J].
Amin, Ketan ;
Dannenfelser, Rose-Marie .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 95 (06) :1173-1176
[2]  
Augustin A. J., 2008, RETINA TODAY, P49
[3]   Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: Applying clinical trial results to the treatment of everyday patients [J].
Brown, David M. ;
Regillo, Carl D. .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 2007, 144 (04) :627-637
[4]   Ranibizumab versus verteporfin for neovascular age-related macular degeneration [J].
Brown, David M. ;
Kaiser, Peter K. ;
Michels, Mark ;
Soubrane, Gisele ;
Heier, Jeffrey S. ;
Kim, Robert Y. ;
Sy, Judy P. ;
Schneider, Susan .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (14) :1432-1444
[5]   Age-related macular degeneration: economic burden and value-based medicine analysis [J].
Brown, MM ;
Brown, GC ;
Stein, JD ;
Roth, Z ;
Campanella, J ;
Beauchamp, GR .
CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE, 2005, 40 (03) :277-287
[6]   Treatment of age-related macular degeneration [J].
Browning, AC ;
Amoaku, WM ;
Dua, HS .
JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, 2004, 97 (04) :166-169
[7]   Poly(N-isopropylacrylamide)-chitosan as thermosensitive in situ gel-forming system for ocular drug delivery [J].
Cao, Yanxia ;
Zhang, Can ;
Shen, Wenbin ;
Cheng, Zhihong ;
Yu, Liangli Lucy ;
Ping, Qineng .
JOURNAL OF CONTROLLED RELEASE, 2007, 120 (03) :186-194
[8]   Age related macular degeneration [J].
Chakravarthy, Usha ;
Evans, Jennifer ;
Rosenfeld, Philip J. .
BMJ-BRITISH MEDICAL JOURNAL, 2010, 340 :526-530
[9]   The iron carrier transferrin is upregulated in retinas from patients with age-related macular degeneration [J].
Chowers, Itay ;
Wong, Robert ;
Dentchev, Tzvete ;
Farkas, Ronald H. ;
Iacovelli, Jared ;
Gunatilaka, Tushara L. ;
Medeiros, Nancy E. ;
Presley, J. Brett ;
Campochiaro, Peter A. ;
Curcio, Christine A. ;
Dunaief, Joshua L. ;
Zack, Donald J. .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (05) :2135-2140
[10]   Development and validation of HPLC method for analysis of dexamethasone acetate in microemulsions [J].
Cocenza Urban, Maria Cristina ;
Mainardes, Rubiana Mara ;
Daflon Gremiao, Maria Palmira .
BRAZILIAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2009, 45 (01) :87-92