Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

Zhuo Ye; Yan-Li Ji; Xiang Ma; Jian-Guo Wen; Wei Wei; Shu-Man Huang

doi:10.3980/j.issn.2222-3959.2015.04.02

Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

Int J Ophthalmol. 2015 Aug 18;8(4):653-8. doi: 10.3980/j.issn.2222-3959.2015.04.02. eCollection 2015.

Authors

Zhuo Ye¹, Yan-Li Ji², Xiang Ma³, Jian-Guo Wen⁴, Wei Wei³, Shu-Man Huang⁴

Affiliations

¹ Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China ; The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China.
² Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China ; Department of Ophthalmology, the Second People's Hospital of Zhengzhou, Zhengzhou 450006, Henan Province, China.
³ Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
⁴ The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China.

PMID: 26309857
PMCID: PMC4539635
DOI: 10.3980/j.issn.2222-3959.2015.04.02

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.

Keywords: bevacizumab-PLGA microspheres; immunohistochemistry; intravitreal injection; pharmacokinetic; sustained release.