Whitney Shatz
Einführung:
Das Auge ist ein einzigartiges Sinnesorgan mit komplexen und komplexen Lebensmechanismen und Physiologie. Es ist hauptsächlich für das Sehen zuständig und wird durch verschiedene Schutzbarrieren geschützt, die von statischen (membranösen) bis hin zu dynamischen (vaskulären) Barrieren reichen. Obwohl diese Barrieren das Auge sehr wirksam vor äußeren Einflüssen und Druck schützen, kann es verschiedene dauerhafte Sehstörungen erleiden, wie z. B. Katarakt, Konjunktivitis, Glaukom, Uveitis, diabetische Retinopathie (DR), diabetisches Makulaödem (DME), altersbedingte Makuladegeneration (AMD), Cytomegalovirus-Retinitis (CMV), Retinitis pigmentosa (RP), retinale Venenblockade (RVO) und Endophthalmitis, die sowohl den vorderen als auch den hinteren Teil des Auges betreffen. Die Behandlung, die erforderlich ist, um die Operationsstelle zu erreichen, wird durch die typischen Barrieren eingeschränkt. Das Schutzorgan wird zu Barrieren, wenn es um die Medikamentenzufuhr geht, insbesondere wenn der hintere Teil des Auges betroffen ist. Die altersbedingte Makuladegeneration ist eine Augenerkrankung, die den hinteren Teil des Auges betrifft und das scharfe Sehvermögen allmählich beeinträchtigt. Dies kann die Lebensqualität erheblich beeinträchtigen. Die intravitreale Injektion ist die bevorzugte Methode zur Verabreichung von Proteintherapeutika in die Augenheilkunde. Der maximale Nutzen wird mit einer Verabreichung alle vier bis zwei Monate erzielt. Eine weniger kontinuierliche Verabreichung würde das Behandlungsgewicht verringern und die Patientenzufriedenheit erhöhen, was die Notwendigkeit von Langzeitverabreichungstechnologien (LAD) mit sich bringt.
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.
Schlussfolgerung und Bedeutung: Obwohl RH-Messungen in vitro für die Vorhersage der Glaskörperhalbwertszeit hilfreich sind, wird die Biokompatibilität der Plattform zunehmend verworren und bleibt ein erhebliches Hindernis für die Entwicklung neuer Technologien.
Biographie:
Whitney Shatz erhielt ihren Master in Biochemie und Molekularbiologie von der University of California in Santa Barbara. Sie beschäftigte sich mit der Charakterisierung bakterieller Enzyme, die am epigenetischen Prozess der DNA-Methylierung beteiligt sind. Seit 2007 arbeitet sie in der Forschungsorganisation von Genentech und unterstützt die Produktion und Charakterisierung von Biologika mit großen Molekülen. Während ihrer elfjährigen Tätigkeit leistete sie bedeutende Beiträge zur Untersuchung der Strukturaktivität/-beziehung bei der antikörperabhängigen Zellzytotoxizität (ADCC) sowie zur Weiterentwicklung neuartiger bispezifischer Antikörper in verschiedenen Krankheitsbereichen. In jüngster Zeit hat sich ihr Schwerpunkt auf die Entwicklung und Charakterisierung von Protein-Polymer-Biokonjugaten für die Verabreichung lang wirkender Arzneimittel verlagert. Darüber hinaus promoviert sie seit 2016 parallel in Pharmazeutischen Wissenschaften an der Universität Genf.
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