惠特尼·沙茨
介紹：
眼睛是非凡的感覺器官，具有複雜而精緻的生命系統和生理機能。通常對視野有幫助，它是透過不同的防禦障礙來保證的；從靜態（膜性）障礙到動態（血管性）障礙。儘管這些邊界非常有效地保護眼睛免受外源性物質和外部壓力的影響，但它是由各種不可逆轉的視力衰弱疾病引起的，例如瀑布、結膜炎、青光眼、葡萄膜炎、糖尿病視網膜病變（DR）、糖尿病黃斑水腫（DME）、老年黃斑部病變（AMD）、鉅細胞病毒（CMV）視網膜炎、色素性視網膜炎（RP）、視網膜靜脈阻塞（RVO）、影響眼睛前部和後部的眼內炎。預計到達活動現場的待遇受到其商標障礙的限制。防禦工具會成為穩定交通的障礙，特別是在眼睛後方出現的情況下。與年齡相關的黃斑部病變是一種影響眼睛後部的眼部疾病，它會逐漸削弱銳利的焦點視力，並可能極大地影響個人滿意度。玻璃體內輸注是蛋白質治療藥物可視化傳遞的首選方案，每 4 個月、每 4 個月給藥一次可達到最大優勢。較少的連續給藥將減輕治療重量並增加耐受一致性，滿足長效傳輸（LAD）進步的要求。
Conveyance of medications to the eye, especially for the treatment of back portion infections, is a difficult undertaking that requires tranquilize transport across boundaries in the eye, which are available to confine the section of medications and xenobiotics. The regular techniques for tranquilize conveyance to the eyedrops, direct infusion, and foundational organization all have issues that limit their handiness, especially for specialists that are high in sub-atomic weight and water-solvent. At present, most visual ailments are treated with the topical utilization of arrangements managed as eye drops for water-dissolvable medications and as salves or watery suspensions for water-insoluble medications. These measurement structures represent approx 90% of right now advertised definitions. The cornea speaks to an essential pathway for visual entrance of topically applied medications. Annular tight intersections (zonula occludens), which totally encompass and viably seal the shallow epithelial cells, make the cornea a powerful obstruction to tranquilize infiltration. Official of medication atoms to corneal tissues additionally seems to upset transcorneal penetratio. Conjunctival infiltration and take-up of topically applied medications is regularly a significant degree higher than corneal take-up. What's more, high tear liquid turnover rates and nasolacrimal seepage add to fast and broad precorneal misfortunes, constraining the adequacy of conjunctival infiltration. Accordingly, after instillation of an eyedrop, under 5% and as meager as 1% of the medication applied enters the cornea and ranges the intraocular tissues. It has been recommended that, after instillation of a drop, the most extreme focus in
the vitreous is roughly one hundred-thousandth that of the drop itself.
Direct infusion of medications into the vitreous hole is in some cases used to accomplish high medication fixations in the vitreous and the retina. Be that as it may, so as to keep up medicate fixations at remedial levels for a delayed timeframe, rehashed infusions are vital, as the half-existence of medications in the vitreous is commonly moderately short. Rehashed infusions bring about patient uneasiness and can conceivably prompt entanglements, for example, vitreous discharge, disease, and focal point or retinal injury. Moreover, the low restorative record of most of the medications utilized for rewarding illnesses of the back portion may require sedate fixations that are at or close to levels poisonous to the retina. Periocular conveyance utilizing subconjuctival or retrobulbar infusions gives an option to intravitreal infusions that is more secure and less obtrusive; this zone has been focused as a possible site for controlled medication conveyance. Fundamental conveyance of ophthalmic medications, while some of the time utilized in the treatment of vitreoretinal illnesses, isn't a powerful option because of the high proficiency of the blood–visual hindrance. The enormous foundational portion required to acquire a remedial degree of medication in the eye seriously constrains the appropriateness of this strategy as a rule; harmfulness in tissues outside the eye is a regular impediment. Moreover, the blood–retinal boundary, which is situated at the degree of retinal vascular endothelial cells and in the retinal shade epithelium, hinders the passage of specific medications from the fundamental dissemination.
In view of these conveyance issues it isn't amazing that, regardless of representing over 55% of every single visual ailment, issues identified with the back portion represent under 5% of the ophthalmic medication showcase. A large portion of the at present accessible clinical treatments for the treatment of sicknesses bringing about loss of sight because of neovascularization in the eye i.e., laser photocoagulation treatment for diabetic retinopathy and photodynamic treatment for age-related macular degeneration utilize either careful mediation or fundamental conveyance of a remedial specialist as the conveyance strategy. The use of novel angiostatic operators, especially proteins or protein-like medications including hostile to vascular endothelial development factor (VEGF), lattice metalloproteinase (MMP) inhibitors, integrin agonists, shade epithelium-inferred factor (PEDF) and inhibitors of insulin-like development factor-1 and development hormone, will require progressively modern techniques for conveyance to guarantee action and adequacy of the medication over a drawn out timeframe and to limit sedate instigated inconveniences. Novel conveyance frameworks are likewise required for therapeutics with a significant level of fundamental poisonousness, for example, steroids. Various epic strategies are being worked on or in clinical use. Gadgets produced using both biostable (nondegradable) and from biodegradable polymers have been researched and examined. Gadgets produced using biodegradable polymers have the favorable position that they corrupt and accordingly vanish from the site of implantation after some time. The potential for additional turn of events, especially for protein operators, is huge; this improvement can exploit information acquired in conveyance of protein medications to different destinations.
Methodology and Theoretical Orientation: Since leeway from the eye is represented essentially by dispersion, restorative Fab was artificially conjugated to different multivalent frameworks by means of maleimide science to increment Fab half-life. Each Fab-conjugate applicant was evaluated dependent on a huge number of criterial including conjugation proficiency, proportion of Fab to transporter, hydrodynamic span, long terms soundness, thickness and action. Now and again, in vivo decency tests were performed to survey biocompatibility with visual tissues.
Findings: Assessment of every framework uncovered characteristics attractive for visual LAD. Frameworks made out of either PEG, HPMA or lipoprotein were viable in expanding Fab RH. Geometry didn't enormously impact RH however affected thickness. Biocompatibility study exhibited bearableness of PEG however not of lipoprotein bearer.
結論與意義：儘管體外 RH 估計對於預測玻璃體半衰期很有價值，但平台生物相容性逐漸變得混亂，並且一直是實現新創新的重大障礙。
傳：
Whitney Shatz 在加州大學聖塔芭芭拉分校獲得生物化學和分子生物學碩士學位，研究 DNA 甲基化表觀遺傳過程中涉及的細菌酶的特性。自 2007 年以來，她一直在基因泰克的研究組織工作，支持大分子生物製劑的生產和表徵。在 11 年的任職期間，她對抗體依賴性細胞毒性 (ADCC) 的結構活性/關係的研究以及各種疾病領域新型雙特異性抗體的進展做出了重大貢獻。最近，她的重點轉向了用於長效藥物傳遞的蛋白質聚合物生物綴合物的開發和表徵。此外，自2016年起，她同時在日內瓦大學攻讀藥學博士學位。
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