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. 2015 Oct 1;8(10):12390-9.
eCollection 2015.

Effect of a new drug releasing system on microencapsulated islet transplantation

Binjie Lu  1 , Qingkun Gao  2 , Rui Liu  3 , Ming Ren  4 , Yan Wu  2 , Zaixing Jiang  5 , Yi Zhou  2
Affiliations

Effect of a new drug releasing system on microencapsulated islet transplantation

Binjie Lu et al. Int J Clin Exp Pathol. .

Abstract

Objective: This study aimed to develop a novel release system for grafted islets.

Materials and methods: A graphene oxide-FTY720 release system was constructed to test the drug loading and releasing capacity. The recipient rats were divided into four groups as following: Experiment group A (EG A) and B (EG B); Control group A (CG A) and B (CG B). In each group, (2000 ± 100) IEQ microencapsulated islets were implanted into the abdominal cavity of the recipients with oral FTY720, local graphene oxide-FTY720 injection, without immunosuppressants, and with graphene oxide-saturated solution respectively. We detected the immunological data, the blood glucose level, and pericapsular overgrowth to show the transplantation effect.

Results: 31% of adsorptive FTY720 was released within 6 h, and 82% of FTY720 was released within 48 h. From day 5 to 8, the amount of PBL in EG B was significantly less than those in EG A (P<0.01). The CD3+ and CD8+ T lymphocytes were suppressed 3 days longer in EG B than in EG A. On day 19 posttransplantation, the blood glucose level in EG B was much lower than that in EG A (P<0.01). On the same day, pericapsular overgrowth was grade I in EG B, grade II in other groups.

Conclusions: Graphene oxide-FTY720 complex showed a drug releasing effect. Local application of graphene-FTY720 releasing system could decrease the amount of peripheral blood lymphocytes (PBL) and the percentage of CD3 and CD8 T lymphocytes in blood for longer time than oral drug application. This releasing system could achieve a better blood glucose control.

Keywords: Islet transplantation; graphene oxide; immunosuppressants; microencapsulation; overgrowth.

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Figures

Figure 1
Figure 1
FTY720 release changing with time. Experiments performed five times.
Figure 2
Figure 2
Activity detection of microencapsulated islets. A. DTZ stain of islets (100×). B. SYTO-green and EB stain of islets (100×). C. Microencapsulated islets (150×). A. The red stain represented the islets; B. The green stain represented live islets, red stain represented dead islets; C. 1-3 islets were encapsulated in one capsule.
Figure 3
Figure 3
A: ΔP<0.01 EG B vs. EG A; *P<0.01 EG B vs. CG B; B: ΔP<0.01 EG B vs. EG A; *P<0.01 EG B vs. CG B; C: ΔP<0.05 EG B vs. EG A; *P<0.01 EG B vs. CG B.
Figure 4
Figure 4
Changes in blood glucose of recipients after transplantation, ΔP<0.01 EG B vs. EG A.; *P<0.01 EG B vs. CG B.
Figure 5
Figure 5
A. Grade of overgrowth, from 0-III grade under light microscope (150×). B. Comparison of the pericapsular overgrowth in both EGs on day 19 posttransplantation (400×). (In each group, two recipients were analyzed) the black arrows represent the yellow stained T lymphocytes, and the white arrows represent the capsules.
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