ABSTRACT
The pentablock (PB) copolymers based composite nanosystems were designed to provide a long-term delivery of macromolecules to the back of the eye. A unique arrangement of each block (polyethylene glycol, polylactic acid, and polycaprolactone) with various molecular weights (PB-A and PB-B) was selected for the synthesis of nanoparticles (NPs) and thermosensitive gel (PB-C) by sequential ring-opening bulk copolymerization reaction. PB copolymers were characterized for their molecular weight and purity by 1H-NMR spectroscopy and crystallinity by PXRD. The macromolecule model drugs [lysozyme (Lyz ~ 14.5 kDa), IgG-Fab (~ 50 kDa), and IgG (~ 150 kDa)] were selected to delineate the effect of molecular weights on in vitro release profile of nanoformulations. Lyz-, Fab-, and IgG-encapsulated NPs were prepared by double emulsion solvent evaporation method. The entrapment efficiency (EE%) and drug loading (DL%) of macromolecules was higher for PB-B copolymers due to its higher molecular weight and hydrophobicity compare to PB-A. The particle size range of NPs was ~ 200-270 nm. In vitro release profiles of Lyz-, Fab-, and IgG-encapsulated in NPs alone and NPs suspended in gel (composite nanosystem) demonstrated a minimal burst release and drug release over a long period. The effect of hydrodynamic diameter of macromolecules and hydrophobicity of PB copolymers was investigated on the release profile of nanosystems. In vitro biocompatibility study showed negligible cytokine (IL-1, IL-6, and TNF-α) release, which confirmed the safety of the PB copolymers. Based on the results, it is anticipated that long-term ocular delivery of macromolecules can be achieved through composite nanosystems.
Subject(s)
Immunoglobulin Fab Fragments , Immunoglobulin G , Muramidase , Nanoparticles , Polymers , Animals , Cytokines/metabolism , Drug Compounding , Drug Liberation , Eye Diseases , Gels , Immunoglobulin Fab Fragments/administration & dosage , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin G/administration & dosage , Immunoglobulin G/chemistry , Mice , Muramidase/administration & dosage , Muramidase/chemistry , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Polymers/administration & dosage , Polymers/chemistry , RAW 264.7 Cells , TemperatureABSTRACT
BACKGROUND: Ocular inflammation and allergic eye diseases range from mild to severe may disturb visual function and affect` quality of life. Since these diseases require intensive therapies, the pathophysiology and treatments of these conditions are highlighted. OBJECTIVE: The ocular diseases caused by inflammation and allergy are extensively studied in this review to provide an overview of the newer compounds, novel delivery approaches, preclinical and clinical trials for the treatment of allergic conjunctivitis, dry eye syndrome, and uveitis. METHOD: The eye is divided into two segments; anterior and posterior. Both segments provide barriers to the drug delivery to the eye. Despite many efforts by scientists, several potential drug candidates are often dropped from the initial screening portfolio due to failure in overcoming these barriers. Thus to overcome unmet challenges, remarkable progresses have been made towards the design of novel ocular therapeutics with enhanced activity and minimal toxicity to the ocular tissue. A comprehensible understanding of the diseased conditions, physiological barriers and pharmacokinetics of the eye would significantly accelerate the development of new therapeutics. Moreover, identification of new targets drives the discovery of novel drug molecules for the ocular disease treatment. RESULTS: The advancement in the drug discovery and dosage from design showcases the increasing number of patent applications being filed and issued for allergic conjunctivitis, dry eye syndrome, and uveitis. In addition, preclinical and clinical trials are now becoming available showing the newer generation of ocular drugs. CONCLUSION: This review presented a brief background on the disease condition, types, treatment, advancement in the delivery approaches, focus on emerging therapeutics, related patents and clinical trials for the treatment of allergic conjunctivitis, dry eye syndrome, and uveitis.
Subject(s)
Conjunctivitis, Allergic/drug therapy , Dry Eye Syndromes/drug therapy , Uveitis/drug therapy , Animals , Conjunctivitis, Allergic/pathology , Drug Delivery Systems , Drug Design , Drug Discovery/methods , Dry Eye Syndromes/pathology , Humans , Inflammation/drug therapy , Inflammation/pathology , Patents as Topic , Quality of Life , Uveitis/pathologyABSTRACT
PURPOSE: To report 2 patients with progressive complex choristomas and to review the literature on this subject. DESIGN: Interventional case reports. METHODS: Clinical and pathologic correlation was performed on 2 patients with progressive epibulbar choristomas. PubMed database was searched to identify all the previously reported cases of progressive epibulbar choristomas (using key words choristoma, dermoid, growth, progression, and evolution). RESULTS: Growth of the epibulbar choristomas was noted in infancy in 1 patient with oculoectodermal syndrome and in puberty in another otherwise healthy patient. Both lesions were identified histopathologically as complex choristomas. In addition to the characteristic choristomatous tissues, both lesions demonstrated increased vascularity, inflammatory infiltrate, and fibroblast proliferation within myxomatous stroma. Review of the literature identified 4 patients with progressive complex choristomas, 1 of whom demonstrated histopathologic findings similar to those of the 2 cases reported here. CONCLUSIONS: Epibulbar choristomas rarely enlarge, likely secondary to reactive changes within the tissue manifested by increased vascularity, inflammatory cell infiltration, and fibroblast proliferation with deposition of myxomatous stroma.
