Modification of Amniotic Membrane as a Depot Carrier for Bevacizumab – An<i>In-Vitro</i>Model for a Slow Release Mechanism

Mayer, Wolfgang J.; Grüterich, Martin; Kook, Daniel; Sigg, W.; Kernt, Marcus; Messmer, Elisabeth M.; Haritoglou, Christos; Wolf, Armin

doi:10.3109/02713683.2012.757326

Cited by 6 publications

(5 citation statements)

References 20 publications

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“…For example, once an appropriate number of tubes have been formed, bevacizumab or other angiogenesis inhibitors can be added to retard the vascularization process before implantation. [49][50][51] As many cell types beyond endothelial cells are involved in vascularization in vivo, it remains to be seen whether these prevascular constructs would remain stable after implantation without accompanying perivascular cells. 52,53 If these additional cells are needed in vitro to ensure success in vivo, the optimum pore size is likely to be slightly larger than the values we report here, as additional space would be needed to facilitate supporting fibroblasts and pericytes.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, tube formation can be maximized and overgrowth minimized by tuning the initial cell density and culture time. For example, once an appropriate number of tubes have been formed, bevacizumab or other angiogenesis inhibitors can be added to retard the vascularization process before implantation . As many cell types beyond endothelial cells are involved in vascularization in vivo , it remains to be seen whether these prevascular constructs would remain stable after implantation without accompanying perivascular cells .…”

Section: Discussionmentioning

confidence: 99%

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Prevascularized silicon membranes for the enhancement of transport to implanted medical devices

et al. 2015

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Recent advances in drug delivery and sensing devices for in situ applications are limited by the diffusion-limiting foreign body response of fibrous encapsulation. In this study, we fabricated pre-vascularized synthetic device ports to help mitigate this limitation. Membranes with rectilinear arrays of square pores with widths ranging from 40 to 200 μm were created using materials (50 μm thick double-sided polished silicon) and processes (photolithography and directed reactive ion etching) common in the manufacturing of microfabricated sensors. Vascular endothelial cells responded to membrane geometry by either forming vascular tubes that extended through the pore or completely filling membrane pores after four days in culture. Although tube formation began to predominate overgrowth around 75 μm and continued to increase at even larger pore sizes, tubes formed at these large pore sizes were not completely round and had relatively thin walls. Thus, the optimum range of pore size for pre-vascularization of these membranes was estimated to be 75 - 100 μm. This study lays the foundation for creating a pre-vascularized port that can be used to reduce fibrous encapsulation and thus enhance diffusion to implanted medical devices and sensors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevascularized silicon membranes for the enhancement of transport to implanted medical devices

et al. 2015

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“…Drug delivery systems have become a hot research topic in order to determine how to prolong the time a drug resides on the eye surface and to improve the bioavailability of drugs [27][28][29]. At present, ophthalmic surface drug delivery systems have been mainly focused on drug-loaded amniotic membranes [30][31][32] and drugloaded corneal contact lens [33][34][35]. Poor transparency and easy dissolution of amniotic membranes means they have limited clinical applications [31].…”

Section: Introductionmentioning

confidence: 99%

“…At present, ophthalmic surface drug delivery systems have been mainly focused on drug-loaded amniotic membranes [30][31][32] and drugloaded corneal contact lens [33][34][35]. Poor transparency and easy dissolution of amniotic membranes means they have limited clinical applications [31]. In addition, studies have shown that drug-loaded corneal contact lenses easily release a large amount of a drug in a short space of time, but they are less likely to meet the requirements of long-term drug release [33,34].…”

Section: Introductionmentioning

confidence: 99%

Carbodiimide crosslinked decellularized lenticules as a drug carrier for sustained antibacterial eye treatments

Rao¹,

Zhou²,

Chen³

et al. 2023

Biomed. Mater.

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In this study, the drug-loading and antibacterial activity of carbodiimide/N-hydroxysuccinimide (EDC/NHS) crosslinked decellularized lenticules (CDLs) were evaluated. Small incision lenticule extraction derived lenticules were decellularized and modified with crosslinking concentrations of 0.00 (E/L00, non-crosslinked), 0.01 (E/L01), 0.05 (E/L05) and 0.25 mmol (E/L25) EDC per mg lenticules at 5:1 EDC/NHS ratios with non-decellularized non-crosslinked lenticules (NDLs) as controls. NDLs and EDC/NHS CDLs had similar water contents. The light transmittance percentages (400–800 nm) were 91.55 ± 1.16%, 88.68 ± 1.19%, 80.86 ± 1.94%, 85.12 ± 2.42% and 85.62 ± 2.84% for NDLs, E/L00, E/L01, E/L05 and E/L25, respectively (P < 0.01). The EDC/NHS CDLs (diameter: 6.36 ± 0.18 mm; central thickness: 117.31 ± 3.46 μm) were soaked in 3% (wt./vol.) levofloxacin (LEV) solution for 3 h. The drug release concentrations of LEV-impregnated EDC/NHS CDLs were determined by high-performance liquid chromatography. Zone inhibition (ZOI) against Staphylococcus aureus of E/L01, E/L05 and E/L25 were superior to E/L00 CDLs (P < 0.01) and among the different crosslinked groups, E/L05 lenticules produced the largest ZOIs and their drug concentration release over 21 d was the highest. EDC/NHS crosslinking can improve the drug-loading effect and antibacterial activity of decellularized lenticules. LEV-impregnated EDC/NHS CDLs are promising drug delivery carriers.

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“…5,6 Yapılan son çalışmalarda, cerrahi öncesi bir süre antibiyotikli sıvıda bekletilen AZ'ın, transplantasyon sonrası yavaş salınımlı ilaç taşıyıcısı gibi davrandığını göstermiş ve AZ için yeni bir potansiyel kullanım alanı tanımlanmıştır. 7 Bu çalışmanın amacı, çeşitli oküler yüzey hastalıklarında kliniğimizde uyguladığımız AZ transplantasyon tekniklerinin sonuçlarını değerlendir mektir.…”

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Outcomes of Amniotic Membrane Transplantation in Corneal Surface Diseases

Kara¹,

Gencer²,

Çömez³

et al. 2016

Turkiye Klinikleri J Ophthalmol

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Ö ÖZ ZE ET T A Am ma aç ç: : Bu çalışmanın amacı, oküler yüzey hastalıklarının tedavisinde uygulanan amniyon zarı (AZ) transplantasyon sonuçlarını değerlendirmektir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Nisan 2011-Ağustos 2015 arasında çeşitli oküler yüzey hastalıkları nedeni ile AZ transplantasyonu uygulanan 28 hastanın 29 gözü ile ilgili dosya arşivi geriye doğru taranarak bu çalışma gerçekleştirildi. Dondurularak saklanmış insan AZ'ları 16 gözde korneanın tamamını örtecek şekilde limbusa yakın 10/0 naylon ile sütüre edildi. Çok katlı uygulamalarda (4 olgu) fibrin doku yapıştırıcısı yardımıyla korneal incelme alanı AZ ile dolduruldu ve üzeri AZ ile örtüldü. Operasyon sonrası terapötik kontakt lens yerleştirildi. Hastaların kontrol muayenelerinde düzeltilmiş en iyi görme keskinliği (DEİGK), kornea epitelizasyon süresi, korneal incelme, enfeksiyon ve nüks varlığı değerlendirildi. B Bu ul lg gu ul la ar r: : Hastaların 18 (%64)'i erkek, 10 (%36)'u kadın idi. Ortalama yaş 62,76±17,47 yıl idi. Hastaların endikasyonları; kimyasal yanık (5 göz), pterjiyum cerrahisi (2 göz), korneal ülser (3 göz), korneal incelme (4 göz), korneal perforasyon (4 göz), büllöz keratopati (4 göz), iyileşmeyen epitel defekti (3 göz), şa-şılık cerrahisi sonrası tenon kisti (2 göz), semblefaron ( 1 göz), skleral incelme (1 göz) şeklindeydi. AZ ile cerrahi 17 gözde örtme, 7 gözde greft ve 5 gözde kombine (greft+örtme) olarak uygulandı. Olguların ortalama takip süresi 10,98±14,62 (1-66) ay ve epitelizasyon süresi 44,77±19,50 gün idi. Preoperatif ortalama DEİGK (1,33±0,52) (LogMAR) ve postoperatif DEİGK (1,22±0,63) arasında anlamlı fark bulunmadı (p=0,148). S So on nu uç ç: : AZ transplantasyonu oküler yüzey hastalıklarında iyileşmeyi kolaylaştıran ucuz, etkin ve güvenilir bir yöntemdir.

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Modification of Amniotic Membrane as a Depot Carrier for Bevacizumab – AnIn-VitroModel for a Slow Release Mechanism

Abstract: In this in-vitro setting, we could demonstrate effective VEGF-blockade for up to 1 week by incubating HAM with bevacizumab. HAMs might be potentially used as a carrier for drugs delivered to the cornea.

Cited by 6 publications

References 20 publications

Prevascularized silicon membranes for the enhancement of transport to implanted medical devices

Prevascularized silicon membranes for the enhancement of transport to implanted medical devices

Carbodiimide crosslinked decellularized lenticules as a drug carrier for sustained antibacterial eye treatments

Outcomes of Amniotic Membrane Transplantation in Corneal Surface Diseases

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