Citation:Ye Z,Ji YL,Ma X,Wen JG,Wei W,Huang SM.Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits.Int J Ophthalmol 2015;8(4):653-658,doi:10.3980/j.issn.2222-3959.2015.04.02
Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits
Received:September 03, 2014  Revised:January 19, 2015
Email this Article  Add to Favorites  Print
DOI:10.3980/j.issn.2222-3959.2015.04.02
Key Words:bevacizumab-PLGA microspheres; intravitreal injection; sustained release; pharmacokinetic; immunohistochemistry
Fund Project:Supported by National Natural Science Foundation of China (No.30973263, No.81370869)
                 
AuthorInstitution
Zhuo Ye Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian , Liaoning Province, China
;The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou , Henan Province, China
Yan-Li Ji Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian , Liaoning Province, China
;Department of Ophthalmology, the Second People’s Hospital of Zhengzhou, Zhengzhou , Henan Province, China
Xiang Ma Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian , Liaoning Province, China
Jian-Guo Wen The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou , Henan Province, China
Wei Wei Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian , Liaoning Province, China
Shu-Man Huang The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou , Henan Province, China
Hits: 643
Download times: 174
Abstract:
      AIM:To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid) (PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.

    METHODS:Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.

    RESULTS:The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form.

    CONCLUSION: The result of this study shows the beneficial effects of PLGA in prolonging the residency of bevacizumab in the vitreous. And the drug delivery system may have potential as a treatment modality for related disease.

PMC FullText Html:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539635/
PDF Fulltext  Download reader  HTML Fulltext   View/Add Comment