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Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes.

Peng Y, Ang M, Foo S, Lee WS, Ma Z, Venkatraman SS, Wong TT - PLoS ONE (2011)

Bottom Line: PLC70/30 15±0.6%; P = 0.91) over a period of 6 months.Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible.The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.

View Article: PubMed Central - PubMed

Affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.

ABSTRACT
Sustained ocular drug delivery is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Biodegradable subconjunctival implants with controlled drug release may circumvent these two problems. In our study, two microfilms (poly [d,l-lactide-co-glycolide] PLGA and poly[d,l-lactide-co-caprolactone] PLC were developed and evaluated for their degradation behavior in vitro and in vivo. We also evaluated the biocompatibility of both microfilms. Eighteen eyes (9 rabbits) were surgically implanted with one type of microfilm in each eye. Serial anterior-segment optical coherence tomography (AS-OCT) scans together with serial slit-lamp microscopy allowed us to measure thickness and cross-sectional area of the microfilms. In vitro studies revealed bulk degradation kinetics for both microfilms, while in vivo studies demonstrated surface erosion kinetics. Serial slit-lamp microscopy revealed no significant inflammation or vascularization in both types of implants (mean increase in vascularity grade PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P = 0.91) over a period of 6 months. Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible. The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.

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Slit-lamp photographs of microfilms after surgical insertion into the subconjunctival space at 1, 3 and 6 months.A, B, C: 1– Slit-lamp photographs of PLGA50/50 microfilm at 1, 3, 6 months respectively. A, B, C: 2 – Slit-lamp photograph of PLC70/30 microfilm at 1, 3, 6 months respectively.
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pone-0022507-g006: Slit-lamp photographs of microfilms after surgical insertion into the subconjunctival space at 1, 3 and 6 months.A, B, C: 1– Slit-lamp photographs of PLGA50/50 microfilm at 1, 3, 6 months respectively. A, B, C: 2 – Slit-lamp photograph of PLC70/30 microfilm at 1, 3, 6 months respectively.

Mentions: The gross appearance and examination of the implanted microfilms revealed minimal localized inflammation and vascularity using serial vascularity grading scales [34] around the implanted PLC70/30 (n = 9) and PLGA50/50 (n = 9). All eyes (n = 18) had mild conjunctival hyperemia and chemosis, which resolved at one week post-operatively (Figure 6). We compared conjunctival vascularity of the insertion site before surgery and at the end of the study in all eyes. We found no significant increase in ocular score in all 18 eyes (mean percent increase in ocular score PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P = 0.91, no significant inter-observer variability). The cornea, anterior chamber and lens remained clear with no evidence of inflammation or scarring. We did notice on external ocular examination that the PLGA50/50 microfilms appeared more pliable compared to the PLC70/30 microfilms, which retained its original shape. However, the animals did not display any signs of ocular discomfort, nor was there any extrusion of any of the implants from either material. At month 4 onwards, the PLGA50/50 microfilms had dissolved to such an extent that they were not grossly visible even with slit-lamp examination. In contrast, PLC70/30 microfilms persisted and visible up to 6 months.


Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes.

Peng Y, Ang M, Foo S, Lee WS, Ma Z, Venkatraman SS, Wong TT - PLoS ONE (2011)

Slit-lamp photographs of microfilms after surgical insertion into the subconjunctival space at 1, 3 and 6 months.A, B, C: 1– Slit-lamp photographs of PLGA50/50 microfilm at 1, 3, 6 months respectively. A, B, C: 2 – Slit-lamp photograph of PLC70/30 microfilm at 1, 3, 6 months respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3142149&req=5

pone-0022507-g006: Slit-lamp photographs of microfilms after surgical insertion into the subconjunctival space at 1, 3 and 6 months.A, B, C: 1– Slit-lamp photographs of PLGA50/50 microfilm at 1, 3, 6 months respectively. A, B, C: 2 – Slit-lamp photograph of PLC70/30 microfilm at 1, 3, 6 months respectively.
Mentions: The gross appearance and examination of the implanted microfilms revealed minimal localized inflammation and vascularity using serial vascularity grading scales [34] around the implanted PLC70/30 (n = 9) and PLGA50/50 (n = 9). All eyes (n = 18) had mild conjunctival hyperemia and chemosis, which resolved at one week post-operatively (Figure 6). We compared conjunctival vascularity of the insertion site before surgery and at the end of the study in all eyes. We found no significant increase in ocular score in all 18 eyes (mean percent increase in ocular score PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P = 0.91, no significant inter-observer variability). The cornea, anterior chamber and lens remained clear with no evidence of inflammation or scarring. We did notice on external ocular examination that the PLGA50/50 microfilms appeared more pliable compared to the PLC70/30 microfilms, which retained its original shape. However, the animals did not display any signs of ocular discomfort, nor was there any extrusion of any of the implants from either material. At month 4 onwards, the PLGA50/50 microfilms had dissolved to such an extent that they were not grossly visible even with slit-lamp examination. In contrast, PLC70/30 microfilms persisted and visible up to 6 months.

Bottom Line: PLC70/30 15±0.6%; P = 0.91) over a period of 6 months.Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible.The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.

View Article: PubMed Central - PubMed

Affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.

ABSTRACT
Sustained ocular drug delivery is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Biodegradable subconjunctival implants with controlled drug release may circumvent these two problems. In our study, two microfilms (poly [d,l-lactide-co-glycolide] PLGA and poly[d,l-lactide-co-caprolactone] PLC were developed and evaluated for their degradation behavior in vitro and in vivo. We also evaluated the biocompatibility of both microfilms. Eighteen eyes (9 rabbits) were surgically implanted with one type of microfilm in each eye. Serial anterior-segment optical coherence tomography (AS-OCT) scans together with serial slit-lamp microscopy allowed us to measure thickness and cross-sectional area of the microfilms. In vitro studies revealed bulk degradation kinetics for both microfilms, while in vivo studies demonstrated surface erosion kinetics. Serial slit-lamp microscopy revealed no significant inflammation or vascularization in both types of implants (mean increase in vascularity grade PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P = 0.91) over a period of 6 months. Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible. The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.

Show MeSH
Related in: MedlinePlus