Concrete Crack Restoration Using Bacterially Induced Calcium Metabolism.

Unlabelled: Concrete structures are prone to develop cracks and cause devastation. Repair and renovation are not enough to ensure complete eradication of crack development. The entire process is costly and laborious.

Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin Absorption Across Ocular Tissues.

The pathophysiological mechanisms for dry and wet age-related macular degeneration (AMD) involve oxidative stress and increased VEGF release and expression. An ideal drug candidate for both types of AMD is the one which offers significant protection to the retinal cells from oxidative stress and inhibit VEGF release. Curcumin is one such natural product which provides numerous beneficial effects including antioxidant, anti-inflammatory, and anti-VEGF activities and has the potential for the treatment of both types of AMD.

In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model.

Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e.

Multi-Layered Nanomicelles as Self-Assembled Nanocarrier Systems for Ocular Peptide Delivery.

Despite the great potential of peptides as therapeutics, there is an unmet challenge in sustaining delivery of sufficient amounts in their native forms. This manuscript describes a novel nanocarrier capable of delivering functional small peptides in its native form. Self-assembling multi-layered nanomicelles composed of two polymers, polyoxyethylene hydrogenated castor oil 40 (HCO-40) and octoxynol 40 (OC-40), were designed to combine hydrophilic interaction and solvent-induced encapsulation of peptides and proteins.

Ocular Pharmacokinetics of a Topical Ophthalmic Nanomicellar Solution of Cyclosporine (Cequa®) for Dry Eye Disease.

Cequa®, a unique and first-in-class preservative free cyclosporine-A (CsA) nanomicellar topical formulation was recently approved by US FDA for treatment of dry eye disease or keratoconjuntivitis sicca (KCS). Being highly hydrophobic, CsA is currently available as an oil based emulsion, which has its own shortcomings. Developing an aqueous and clear formulation of CsA is imperative yet a challenging need in the quest for a safe and better drug product.

Novel Random Triblock Copolymers for Sustained Delivery of Macromolecules for the Treatment of Ocular Diseases.

The objective of this study is to design, develop, and synthesize novel random triblock (RTB) copolymers for sustained delivery of macromolecules. RTB copolymers have not been utilized for the delivery of macromolecules for ocular diseases. RTB copolymers comprising of polyethylene glycol, glycolide, and ɛ-caprolactone blocks were synthesized and assessed for their molecular weights and purity using H-NMR spectroscopy, gel permeation chromatography, FTIR (functionality), and XRD (crystallinity).

PSMA Antibody-Conjugated Pentablock Copolymer Nanomicellar Formulation for Targeted Delivery to Prostate Cancer.

The main purpose of this study was to develop a prostate-specific membrane antigen (PSMA) antibody-conjugated drug-loaded nanomicelles using MPEG--PLA-PCL-PLA-PEG-NH2 pentablock copolymer for targeted delivery of hydrophobic anticancer drugs to prostate cancer cells. During this experiment, monomers of L-lactide, ε-caprolactone, poly(ethylene glycol)-methyl ether, and poly(ethylene glycol)-NH2 were used to prepare pentablock copolymer using the ring opening technique. The pentablock nanomicellar (PBNM) formulation was prepared by the evaporation-rehydration method.

Strategic Pentablock Copolymer Nanomicellar Formulation for Paclitaxel Delivery System.

Nanomicelles (NM) enhance solubility and absorption of active pharmaceutical ingredients (APIs). Various polymers and non-polymers are utilized to prepare nanomicellar formulations to achieve high absorption and delivery of drugs. The main purpose of this study was to develop drug-loaded nanomicelles with pentablock copolymers for paclitaxel delivery.

The relationship between outflow resistance and trabecular meshwork stiffness in mice.

It has been suggested that common mechanisms may underlie the pathogenesis of primary open-angle glaucoma (POAG) and steroid-induced glaucoma (SIG). The biomechanical properties (stiffness) of the trabecular meshwork (TM) have been shown to differ between POAG patients and unaffected individuals. While features such as ocular hypertension and increased outflow resistance in POAG and SIG have been replicated in mouse models, whether changes of TM stiffness contributes to altered IOP homeostasis remains unknown.

Ocular delivery of proteins and peptides: Challenges and novel formulation approaches.

The impact of proteins and peptides on the treatment of various conditions including ocular diseases over the past few decades has been advanced by substantial breakthroughs in structural biochemistry, genetic engineering, formulation and delivery approaches. Formulation and delivery of proteins and peptides, such as monoclonal antibodies, aptamers, recombinant proteins and peptides to ocular tissues poses significant challenges owing to their large size, poor permeation and susceptibility to degradation. A wide range of advanced drug delivery systems including polymeric controlled release systems, cell-based delivery and nanowafers are being exploited to overcome the challenges of frequent administration to ocular tissues.

Nanoparticles in thermosensitive gel based composite nanosystem for ocular diseases.

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 H-NMR spectroscopy and crystallinity by PXRD.

Recent Patents and Emerging Therapeutics on Ocular Inflammation and Allergy.

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.

Pentablock copolymer dexamethasone nanoformulations elevate MYOC: in vitro liberation, activity and safety in human trabecular meshwork cells.

Aim: The aim of this study is to examine the elevation of MYOC in long-term treatment of human trabecular meshwork (HTM) cells using dexamethasone (DEX) encapsulated pentablock (PB) copolymer-based nanoparticles (NPs) (DEX-PB-NPs).

Materials & Methods: PB copolymers and DEX-PB-NPs were synthesized and characterized using nuclear magnetic resonance, gel permeation chromatography, and X-ray diffraction analyses. MYOC levels secreted from HTM cells were measured by western blot (WB) analysis.

Topical Formulation of Self-Assembled Antiviral Prodrug Nanomicelles for Targeted Retinal Delivery.

Topical drug administration for back of the eye delivery is extremely challenging due to the presence of protection mechanisms and physiological barriers. Self-assembled polymeric nanomicelles have emerged as promising vehicles for drug delivery. Apart from serving as an inert nanocarrier for therapeutic agents, polymeric nanomicelles are known to bypass mononuclear phagocytic system (MPS) and efflux transporters thereby improving drug bioavailability.

Clear, Aqueous Topical Drop of Triamcinolone Acetonide.

The objective of this study was to develop a clear aqueous mixed nanomicellar formulation (NMF) of triamcinolone acetonide (TA) with a combination of nonionic surfactant hydrogenated castor oil 60 (HCO-60) and octoxynol-40 (Oc-40). In order to delineate the effects of drug-polymer interactions on entrapment efficiency (EE), loading efficiency (LE), and critical micellar concentration (CMC), a design of experiment (DOE) was performed to optimize the formulation. In this study, full-factorial design has been used with HCO-60 and OC-40 as independent variables.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials.

How are we improving the delivery to back of the eye? Advances and challenges of novel therapeutic approaches.

Drug delivery to the back of the eye requires strategic approaches that guarantee the long-term therapeutic effect with patient compliance. Current treatments for posterior eye diseases suffer from significant challenges including frequent intraocular injections of anti-VEGF agents and related adverse effects in addition to the high cost of the therapy. Areas covered: Treatment challenges and promising drug delivery approaches for posterior segment eye diseases, such as age-related macular degeneration (AMD) are summarized.

A comprehensive insight on ocular pharmacokinetics.

The eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment models of ocular drug delivery have been developed for describing the absorption, distribution, and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye.

Uptake and bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir by nanoparticulate carriers in corneal epithelial cells.

Purpose: The objective of this study is to investigate cellular uptake of prodrug-loaded nanoparticle (NP). Another objective is to study bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and d-Val-l-Val-GCV (DLGCV) in human corneal epithelial cell (HCEC) model.

Methods: Poly(-lactic-co-glycolic acid) (PLGA) NP encapsulating prodrugs of GCV were formulated under a double emulsion method.

Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir.

Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity.

Recent perspectives on the delivery of biologics to back of the eye.

Biologics are generally macromolecules, large in size with poor stability in biological environments. Delivery of biologics to tissues at the back of the eye remains a challenge. To overcome these challenges and treat posterior ocular diseases, several novel approaches have been developed.

Circumvention of P-gp and MRP2 mediated efflux of lopinavir by a histidine based dipeptide prodrug.

Purpose: This study was aimed to develop a novel Histidine-Leucine-Lopinavir (His-Leu-LPV) dipeptide prodrug and evaluate its potential for circumvention of P-gp and MRP2-mediated efflux of lopinavir (LPV) indicated for HIV-1 infection.

Methods: His-Leu-LPV was synthesized following esterification of hydroxyl group of LPV and was identified by (1)H NMR and LCMS/MS techniques. Aqueous solubility, stability and cell cytotoxicity of prodrug was determined.

Transporter effects on cell permeability in drug delivery.

The role of drug transporters as one of the determinants of cellular drug permeability has become increasingly evident. Despite the lipophilicity of a drug molecule as rate-limiting factor for passive diffusion across biological membranes, carrier-mediated and active transport have gained attention over the years. A better understanding of the effects and roles of these influx transporters towards transmembrane permeability of a drug molecule need to be delineated for drug development and delivery.