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Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically acti...
Context in source publication
Context 1
... with specific physio- logical functions makes it a very distinct organ [1][2][3]. Human eye can be generally divided into the anterior and the poste- rior segments. The anterior segment includes the cornea, conjunctiva, iris, ciliary body, aqueous humor and lens while the posterior segment comprises sclera, choroid, retina and vitreous humor Fig. (1). Cornea, the outermost transparent multilayered membrane of the eye, is devoid of blood supply and acquires its nourishment from aqueous humor and limbal blood capillaries [4]. The human cornea is comprised of five layers i.e. corneal epithelium, Bowman's membrane, stroma, Descemet's membrane, and endothelium. The aqueous hu- mor is a ...
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Purpose:
The neonatal Fc receptor (FcRn) plays a critical role in the homeostasis and degradation of immunoglobulin G (IgG). It mediates the transport of IgG across epithelial cell barriers and recycles IgG in endothelial cells back into the bloodstream. These functions critically depend on the binding of FcRn to the Fc domain of IgG. The half-lif...
Citations
... According to the inventors, these pharmaceutically acceptable carriers can be delivered by topical, intravitreal, subretinal, periocular, subconjunctival, intracanalicular, transscleral, intracameral, retrobulbar, or suprachoroidal methods. Another patent that has been issued for the management of glaucoma has been tabulated in Table 5. 112 FDA approval of the first commercially available ophthalmic nanoemulsion for the administration of 0.05% cyclosporine A (Restasis ® ) for dry eye treatment occurred in 2002. An anionic nanoemulsion without preservatives is called Restasis ® . ...
Glaucoma is a progressive visual polyneuropathy characterized by retinal ganglion cell atrophy and optic nerve head changes. It's generally triggered due to increased intraocular pressure compared with the healthy eye. Glaucoma is treated with various medications in traditional eye drops, such as prostaglandins, carbonic anhydrase inhibitors, beta-blockers, and others. Such treatments are difficult to use and produce lachrymal leakage and inadequate corneal permeability, resulting in lower availability. Ophthalmic in situ gels, introduced in past decades with tremendous effort, are among the finest various choices to solve the drawbacks of eye drops. Employing different polymers with pH-triggered, temperature-triggered, and ion-activated processes have been used to generate ophthalmic in situ gelling treatments. Once those preparations are delivered into the eye, they change phase from sol to gel, allowing the medicine to stay in the eye for longer. These formulations are known as smart gels as they turn into gelling fluids when administered into the eyes. The different mechanisms of in situ gel formulations are used for the management of glaucoma and are discussed in this review article.
... Effective ocular drug delivery is one of the most challenging tasks facing pharmaceutical scientists as the anatomy, physiology, and biochemistry of the eye combine to produce a unique structure that limits the entry of drug molecules (Dutt Vadlapudi et al., 2012). ...
The objective of this study was to develop and evaluate an effective topical formulation to promote corneal epithelial wound healing. Ascorbyl glucoside (AA-2G), a stable prodrug of AA, was formulated in solid in oil (S/O) nanodispersions by emulsifying AA-2G solutions in cyclohexane using Span 85 as an emulsifying agent and freeze-drying emulsions to produce AA-2G – surfactant complex. The complexes were then dispersed in castor oil to produce S/O nanodispersions which were evaluated in terms of their particle size, polydispersity index, encapsulation efficiency, morphology, physical stability as well as the transcorneal permeation and accumulation of AA-2G. The same preparation procedure was used to prepare S/O nanodispersions of AA. S/O nanodispersions of AA and AA-2G were formulated into oily drops that were tested for efficacy in promoting wound healing after corneal epithelial depredation.
AA-2G was loaded efficiently in S/O nanodispersions (EE >99%) in the form of spherical nanoparticles. S/O nanodispersions were physically stable and resulted in improved permeation (18x) and accumulation (7x) of AA-2G in transcorneal diffusion experiments in comparison to AA-2G solutions. Oily eye drops of AA-2G and AA showed no irritation and significant improvement in epithelial healing in vivo in comparison to AA-2G and AA solutions.
... Cross-sectional anatomy of the eye[12] ...
Abstract Allergic eye disease is common, yet often overlooked in North America. In the U.S., up to 40% of the population is deemed to be affected and this number is growing. Symptoms and signs of ocular allergy can lead to decreased productivity and negatively impact quality of life (QoL). Various treatment options exist to achieve symptom control. For allergic conjunctivitis, ophthalmic agents include antihistamines, mast cell stabilizers, dual-activity agents, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and some off-label treatments. Immunotherapy is recommended as a therapeutic option. This review provides a summary of the forms of ocular allergies, with a focus on symptoms and signs, impact on QoL, physical examination, diagnosis and therapeutic options of allergic conjunctivitis. Through multidisciplinary collaborations, a simplified algorithm for the treatment of allergic conjunctivitis is proposed for Canadian clinical practice.
... Drug delivery in humans remains a challenge, and the negative results observed in trials thus far may be explained by the naked small interfering RNA delivery system, which is different from the system used in animals. Bevasiranib is an interesting technology and a promising drug based on pharmaceuticals (74,75) . ...
Age-related macular degeneration is the leading cause of vision loss in elderly individuals, as well as a medical and socio-economic challenge. The treatment of dry age-related macular degeneration is based on vitamin supplementation. New treatment studies are focused on preventing the progression of degeneration and repopulating the atrophic macula. Recently, research on the treatment of neovascular age-related macular degeneration experienced a breakthrough with the advent of anti-vascular endothelial growth factor inhibitors. Nevertheless, despite the fact that ranibizumab, aflibercept, and bevacizumab are effective in reducing severe visual impairment, patients usually lose some vision over time. Therefore, the search for new therapies and diagnostic methods is fundamentally important. Current studies are focused on new anti-vascular endothelial growth factor drugs, nucleoside reverse transcriptase inhibitors, antibody against sphingosine-1-phosphate, anti-platelet-derived growth factor, gene therapy, and RNA interference. The results of ongoing clinical studies may improve the therapy of age-related macular degeneration.
... [11] Although CA inhibitors such as dorzolamide and brinzolamide have been used to reduce intra-ocular pressure (IOP), several drawbacks such as undesired side effects have limited their application. [12,20,21] hCA IV is a membrane bound isoform and its deregulated activity is associated with glaucoma, retinitis pigmentosa and stroke. [17] hCA IX, a transmembrane isoform, takes part in tumor growth, metastases and cancer stem cell population dynamics, mainly leading to acidification of extracellular environment and several other processes related to tumorigenesis. ...
In the present study, a planning strategy for N-substituted-5-
arylidenerhodanines was developed by the condensation
between 3-morpholinopropan-1-amine, aldehyde, ethyl bromoacetate and carbon disulfide in the presence of trimethylamine in water via a one-pot, sequential four component
reaction at room temperature and additionally microwave and
ultrasound irradiated techniques. The synthesis of arylidenerhodanine derivatives was performed through the optimized one
pot strategy starting from commercially available materials in
high yields and purity without troublesome work-ups, after
recrystallization from an appropriate solvent. Enzyme inhibition
activity screening studies on CA II was also carried out. IC50
values of some of examined molecules could be determined
and it was observed that they were nanomolar level except for
1r, and lower than that of reference molecule. The inhibition in
the range of 8.6-99.4% was seen in the presence of newly
synthesized molecules at their reachable maximum concentration in the reaction mixtures. Among the examined molecules, 5a and 5p with the two lowest IC50 values were found to
be the most potent inhibitors. In silico studies showed that all
of the rhodanine derivatives have higher affinity than reference
ligand against binding site, while none of the compounds have
demonstrated any interaction with Zn2+ as with the classical
sulfonamides.
... The shape and size of surfactant micelles depend on the concentration of surfactants, pH, temperature and the ionic strength of the surfactant. Nanomicelles have the following advantages: minimal drug degradation, easy permeation through the ocular epithelium, enhanced bioavailability and no irritation (Cholkar et al. 2012). ...
... However, many drawbacks limit the widespread use of ocular protein delivery due to poor eye membrane permeability, hydrophilic property and macromolecular structures of proteins, and the presence of many enzymes in the eye such as protease and amino peptidase that can degrade the proteins and peptides being administered. Several strategies have been used to improve the bioavailability of proteins and peptides as described below (Mitragotri et al. 2014;Vadlapudi et al. 2012). ...
Drugs for ocular administration are administered topically and their absorption is limited by different barriers known as ocular barriers. These barriers are located in different areas of the eye and the barrier encountered by a particular drug will depend on the route of administration of the drug to the eye, or the segment of the eye the drug is eliciting its action. Some of these barriers include tear film, the blood-ocular barrier which consists of blood-aqueous barrier and blood-retinal barrier and tight junctions present in the cornea that prevents passage of some drug molecules. This chapter will discuss the physiological barriers to ocular drug delivery which limit the distribution of the drug within the eye and also reduce its bioavailability.
... It is more comfortable and patient-compliant than dorzolamide (2.0%) [17]. Common side effects associated with topical dorzolamide and brinzolamide include local irritation, stinging, skin rash, redness, pruritus, blurred vision and corneal decompensation [18]. Initially several CAI derivatives were synthesized to improve solubility, ocular tissue permeation and to overcome such adverse effects [19]. ...
Introduction:
Glaucoma is a neurodegenerative disease with heterogeneous causes that result in retinal ganglionic cell (RGC) death. The discovery of ocular antihypertensives has shifted glaucoma therapy, largely, from surgery to medical intervention. Indeed, several intraocular pressure (IOP)-lowering drugs, with different mechanisms of action and RGC protective property, have been developed.
Areas covered:
In this review, the authors discuss the main new class of kinase inhibitors used as glaucoma treatments, which lower IOP by enhancing drainage and/or lowering production of aqueous humor. The authors include novel inhibitors under preclinical evaluation and investigation for their anti-glaucoma treatment. Additionally, the authors look at treatments that are in clinics now and which may be available in the near future.
Expert opinion:
Treatment of glaucoma remains challenging because the exact cause is yet to be delineated. Neuroprotection to the optic nerve head is undisputable. The novel Rho-associated kinase inhibitors have the capacity to lower IOP and provide optic nerve and RGC protection. In particular, the S-isomer of roscovitine has the capacity to lower IOP and provide neuroprotection. Combinations of selected drugs, which can provide maximal and sustained IOP-lowering effects as well as neuroprotection, are paramount to the prevention of glaucoma progression. In the near future, microRNA intervention may be considered as a potential therapeutic target.
... Currently, ocular route is mainly used for the delivery of proteins and peptides for the treatment of local ocular disorders such as age related macular degeneration, dry eye disease, or proliferative diabetic retinopathy. Lucentis ® and Eylea ® are the recently marketed proteins intended for the treatment of ocular diseases [9,168]. The physiological and anatomical barriers and enzymatic degradation within the ocular environment limit the efficacy of proteins and peptides administered by ocular route [169]. ...
Proteins and peptides are widely indicated in many disease states. Parenteral route is a most commonly employed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patience compliance. Non-invasive routes such as nasal, pulmonary, transdermal and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transdermal, and ocular administrations.
... Delivery of pharmacologically active drugs at therapeutic concentrations to the target tissues with minimal/no toxicity to the healthy ocular tissues still remains a significant challenge for ocular pharmacologists. The complex anatomy and physiology of the eye restricts drug entry to the desired site of action, thus rendering it a highly protected organ [1]. Furthermore, existence of static and dynamic barriers, including the lipophilic corneal epithelium, hydrophilic corneal and scleral stroma, conjunctival lymphatics, choroidal vasculature and blood-ocular barriers, also pose a significant challenge for ocular drug absorption [2,3]. ...
... Moreover, it is largely associated with a growing risk of tissue damage, infection and serious adverse effects. Therefore, a successful topical formulation enabling drug delivery to the front-and back-of-theeye would redefine ocular drug delivery and provide opportunities to address large markets, including dry eye syndrome, glaucoma, agerelated macular degeneration, cytomegalovirus retinitis, diabetic retinopathy and other inherited retinal degenerative diseases [1,[7][8][9][10][11]. Several drugs are currently available for effective treatment of ocular disorders. ...
... Therapeutic Delivery (2013) 4 (1) retinopathy, diabetic macular edema and posterior uveitis. It is highly anticipated that nanomicelles as potential drug-delivery systems may receive US FDA approval for human use in the near future. ...
... 6 Inflammation is commonly associated with ocular pathologies such as, but not limited to, uveitis, immune rejection of corneal transplants, dry eye syndrome, keratitis, age-related macular degeneration, and retinitis. 7 To treat such chronic conditions, sustained drug delivery systems are required. Currently, such inflammatory conditions are treated with repeated topical applications, preferably eye drops. ...
Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches.
