Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post-injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post-injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.
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PMID:Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses. 1900 Feb 72

Following intravitreal (IVT) injection, therapeutic proteins get exposed to physiological pH, temperature and components in the vitreous humor (VH) for a significantly long time. Therefore, it is of interest to study the stability of the proteins in the VH. However, the challenge posed by the isolated VH (such as pH shift upon isolation and incubation due to the formation of smaller molecular weight (MW) degradation products) can result in artefacts when investigating protein stability in relevance for the actual in vivo situation. In this current study, an ex-vivo intravitreal horizontal stability model (ExVit-HS) has been successfully developed and an assessment of long-term stability of a bi-specific monoclonal antibody (mAb) drug in the isolated VH for 3months at physiological conditions has been conducted. The stability assessment was performed using various analytical techniques such as microscopy, UV visible for protein content, target binding ELISA, Differential Scanning Calorimetry (DSC), Capillary-electrophoresis-SDS, Size Exclusion (SEC) and Ion-exchange chromatography (IEC) and SPR-Biacore. The results show that the ExVit-HS model was successful in maintaining the VH at physiological conditions and retained a majority of protein in the VH-compartment throughout the study period. The mAb exhibited significantly less fragmentation in the VH relative to the PBS control; however, chemical stability of the mAb was equally compromised in VH and PBS. Interestingly, in the PBS control, mAb showed a rapid linear loss in the binding affinity. The loss in binding was almost 20% higher compared to that in VH after 3months. The results clearly suggest that the mAb has different degradation kinetics in the VH compared to PBS. These results suggest that it is beneficial to investigate the stability in the VH for drugs intended for IVT injection and that are expected longer residence times in the VH. The studies show that the ExVit-HS model may become a valuable tool for evaluating stability of protein drugs and other molecules following IVT injection.
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PMID:Prediction of intraocular antibody drug stability using ex-vivo ocular model. 2786 34