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Development of Ophthalmic Formulations
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Paramita Sarkar, Martin Coffey, Mohannad Shawer
This is an important and promising route of delivering compounds to the back of the eye. It includes subconjunctival, peribulbar, retrobulbar, and subtenon injections. In all these injections, the major permeability and loss to the systemic circulation limitations through the conjunctiva is avoided. Additionally, the drug has more time to diffuse through the sclera to the choroids and retina than that with topical administration. Scleral permeability, as discussed before, is not affected by lipophilicity of the compound but with the molecular radius. Large molecules up to 70 kDa are still able to penetrate the sclera [44]. The large surface area of the sclera offers great potential for both small and large molecules to diffuse into the choroids, retina, and vitreous. In the periocular delivery, drug release from various delivery systems and elimination is depicted in Figure 13.6. Once drug molecules diffuse through the sclera, they have to diffuse through the suprachoroidal space to the choriocapillaris and then through Bruch’s membrane to the RPE (outer retina–blood barrier). The major limitation of drug to diffuse to the retina is the RPE. The majority of drug dissolved or released will be lost to non-ocular tissue and eventually to the systemic circulation. Minimal loss to the choroidal circulation is expected [45]. The ability of the nanoparticles to penetrate through the sclera–choroid–retina has been recently reported to have nonsignificant transport across these tissues with the majority of the nanoparticles being lost to periocular circulation and lymphatics [46]. Differences between the various injections (subconjunctival, peribulbar, retrobulbar, and subtenon) exist with regard to penetration into posterior tissues [47]. More drug is available in the vitreous and subretinal fluid when given as a subconjunctival injection compared to peribulbar injection [48,49]. This can be due to the close proximity to the eye in cases of subconjunctival injection. Subtenon injection is also utilized for the delivery of active compounds behind the macula for effective delivery to the choroids and retina. The advantage of this injection is the potential ability of Tenon’s capsule to capture the delivery system (suspension, microspheres, or nanoparticles) in place where drug release/dissolution will continue for an extended period of time. The transscleral route is most promising and less-invasive route when compared to intravitreal delivery, especially with the advancement in the controlled-release delivery systems.
Traffic-related particulate matter aggravates ocular allergic inflammation by mediating dendritic cell maturation
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Moonwon Hwang, Sehyun Han, Jeong-Won Seo, Ki-Joon Jeon, Hyun Soo Lee
This model was previously described by Schlereth et al. (2012). DCs in the draining cervical LNs of mice applied topically twice a day for 7 days with either PM2.5 (N = 20 per each experiment) or vehicle (N = 20 per each experiment) were isolated with anti-CD11c magnetic-beads sorting according to manufacturer’s instructions (#130-108-338, Miltenyi Biotec, Germany). Approximately 90% purity was achieved for purified CD11c+ cells, which were washed and prepared for subconjunctival injection. Host mice were sensitized by ip injection of OVA and anesthetized for the unilateral subconjunctival injection of purified CD11c+ DCs (0.5 × 104 in 10 µl sterile HBSS) 2 weeks later. A topical OVA (250 µg/5 µl) instillation was followed by the subconjunctival injection of DCs and the OVA eye drops were administered once daily for 9 days.