Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin.

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development.

On the role of excipients in biopharmaceuticals manufacture: Modelling-guided formulation identifies the protective effect of arginine hydrochloride excipient on spray-dried Olipudase alfa recombinant protein.

Biopharmaceuticals are labile biomolecules that must be safeguarded to ensure the safety, quality, and efficacy of the product. Batch freeze-drying is an established means of manufacturing solid biopharmaceuticals but alternative technologies such as spray-drying may be more suitable for continuous manufacturing of inhalable biopharmaceuticals. Here we assessed the feasibility of spray-drying Olipudase alfa, a novel parenteral therapeutic enzyme, by evaluating some of its critical quality attributes (CQAs) in a range of excipients, namely, trehalose, arginine (Arg), and arginine hydrochloride (Arg-HCl) in the sucrose/methionine base formulation.

Improving corneal permeability of dexamethasone using penetration enhancing agents: First step towards achieving topical drug delivery to the retina.

With an ever-increasing burden of vision loss caused by diseases of the posterior ocular segment, there is an unmet clinical need for non-invasive treatment strategies. Topical drug application using eye drops suffers from low to negligible bioavailability to the posterior segment as a result of static and dynamic defensive ocular barriers to penetration, while invasive delivery systems are expensive to administer and suffer potentially severe complications. As the cornea is the main anatomical barrier to uptake of topically applied drugs from the ocular surface, we present an approach to increase corneal permeability of a corticosteroid, dexamethasone sodium-phosphate (DSP), using a novel penetration enhancing agent (PEA).

Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery: stability, , and analyses.

Background: Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles.

Methods: Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid with garlic (GL) and ginger (GR) oils, separately.

Development of a rapid quantitative method of analysis of carbohydrate fatty acid ester reaction mixtures using H qNMR.

Two new analytical methods, applying absolute H qNMR, were developed to monitor product yield and quantify unreacted carbohydrate and fatty acid reactants, in the synthesis of carbohydrate fatty acid esters (CFAE). These methods provide a mass balance of the crude reaction mixtures and diversify the analytical screening and quantitation approaches available within the synthesis of these molecules. Both methods were validated for the model reaction of methyl α-d-glucopyranoside (MAG) and lauric acid (LA) to form the mono ester product, methyl 6-O-dodecanoyl-α-d-glucopyranoside.

General aspects of powder rheology applied to pharmaceutical formulations.

Powder flowability is crucial in the pharmaceutical industry, strongly affecting solid dosage processing. Classical experimental techniques offer straightforward results for the rapid screening of formulations during development. However, they fail to describe powder properties under consolidation.

Design of liposomal nanocarriers with a potential for combined dexamethasone and bevacizumab delivery to the eye.

Clinicians face numerous challenges when delivering medications to the eyes topically because of physiological barriers, that can inhibit the complete dose from getting to the intended location. Due to their small size, the ability to deliver drugs of different polarities simultaneously, and their biocompatibility, liposomes hold great promise for ocular drug delivery. This study aimed to develop and characterise a dual loaded liposome formulation encapsulating Bevacizumab (BEV) and Dexamethasone (DEX) that possessed the physicochemical attributes suitable for topical ocular delivery.

Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance.

Wet age-related macular degeneration (wAMD) is a chronic inflammation-associated neurodegenerative disease affecting the posterior part of the eye in the aging population. Aging results in the reduced functionality of cells and tissues, including the cells of the retina. Initiators of a chronic inflammatory and pathologic state in wAMD may be a result of the accumulation of inevitable metabolic injuries associated with the maintenance of tissue homeostasis from a young age to over 50.

NAD+-associated-hyaluronic acid and poly(L-lysine) polyelectrolyte complexes: An evaluation of their potential for ocular drug delivery.

This study details the formation and characterisation of a novel nicotinamide adenine dinucleotide (NAD+)-associated polymeric nanoparticle system. The development of a polyelectrolyte complex (PEC) composed of two natural polyelectrolytes, hyaluronic acid and poly(L-lysine), and an evaluation of its suitability for NAD+ ocular delivery, primarily based on its physicochemical properties and in vitro release profile under physiological ocular flow rates, were of key focus. Following optimisation of formulation method conditions such as complexation pH, mode of addition, and charge ratio, the PEC was successfully formulated under mild formulation conditions via polyelectrolyte complexation.

Quality by design - Spray drying of ciprofloxacin-quercetin fixed-dose combination intended for inhalation.

Spray drying is a well-suited technique for producing fixed-dose drug combinations. There has been a growing interest in utilizing spray drying to engineer carrier-free inhalable drug particles. The aim of this study was to understand and optimise the spray drying process of a ciprofloxacin-quercetin fixed dose combination intended for pulmonary administration.

Circulating inflammatory biomarker responses in intervention trials in frail and sarcopenic older adults: A systematic review and meta-analysis.

Consistent with the inflammaging concept, cross-sectional associations have been established between inflammatory biomarkers, frailty and sarcopenia. Less certain is the value of inflammatory markers in monitoring potential anti-inflammatory effects of therapeutic interventions targeted at frailty and sarcopenia. The aims of this systematic review and meta-analysis are to determine if there is a measurable change in inflammatory or immune biomarkers in interventions that improve frailty or sarcopenia and 2.

Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering.

Biopharmaceuticals are large, complex and labile therapeutic molecules prone to instability due to various factors during manufacturing. To ensure their safety, quality and efficacy, a wide range of critical quality attributes (CQAs) such as product concentration, aggregation, particle size, purity and turbidity have to be met. Size exclusion chromatography (SEC) is the gold standard to measure protein aggregation and degradation.

Recent Advances in Ophthalmic Drug Delivery.

Due to population aging and to the increasing prevalence of diseases such as diabetes, chronic eye disorders such as glaucoma, age-related macular degeneration, and diabetic retinopathy have increased significantly, becoming responsible for a high percentage of blindness and vision impairment cases at a global level [...

Hyaluronic Acid: Its Versatile Use in Ocular Drug Delivery with a Specific Focus on Hyaluronic Acid-Based Polyelectrolyte Complexes.

Extensive research is currently being conducted into novel ocular drug delivery systems (ODDS) that are capable of surpassing the limitations associated with conventional intraocular anterior and posterior segment treatments. Nanoformulations, including those synthesised from the natural, hydrophilic glycosaminoglycan, hyaluronic acid (HA), have gained significant traction due to their enhanced intraocular permeation, longer retention times, high physiological stability, inherent biocompatibility, and biodegradability. However, conventional nanoformulation preparation methods often require large volumes of organic solvent, chemical cross-linkers, and surfactants, which can pose significant toxicity risks.

Using deep learning to detect digitally encoded DNA trigger for Trojan malware in Bio-Cyber attacks.

This article uses Deep Learning technologies to safeguard DNA sequencing against Bio-Cyber attacks. We consider a hybrid attack scenario where the payload is encoded into a DNA sequence to activate a Trojan malware implanted in a software tool used in the sequencing pipeline in order to allow the perpetrators to gain control over the resources used in that pipeline during sequence analysis. The scenario considered in the paper is based on perpetrators submitting synthetically engineered DNA samples that contain digitally encoded IP address and port number of the perpetrator's machine in the DNA.

The influence of poly(allylamine hydrochloride) hydrogel crosslinking density on its thermal and phosphate binding properties.

Sevelamer hydrochloride (SH) or Renagel® is an effective phosphate binder prescribed to prevent the absorption of phosphate in end stage renal disease (ESRD) patients. The relationship between SH structure and binding capacity and affinity is very important and can be used in characterising the sensitivity of the hydrogel to binding conditions. Thus, a series of hydrogels were prepared by varying the amount of crosslinker, whilst the other hydrogel components were kept constant.

Particle Engineering by Nano Spray Drying: Optimization of Process Parameters with Hydroethanolic versus Aqueous Solutions.

Nano spray drying has emerged as an outstanding platform for engineering micro- and nanoparticles, with growing applications in various areas of drug delivery. As a new technology involving distinct technical design, parameters of the nano spray drying process are not fully elucidated. In a quality-by-design approach, the aim of the current study was to gain thorough understanding of critical determinants of product characteristics in the Büchi Nano Spray Dryer B-90.

Development and characterization of a spray-dried inhalable ciprofloxacin-quercetin co-amorphous system.

Spray drying is an increasingly used particle engineering technique for the production of dry powders for inhalation. However, the amorphous nature of most spray-dried particles remains a big challenge affecting both the chemical and the physical stability of the dried particles. Here, we study the possibility of producing co-amorphous ciprofloxacin-quercetin inhalable particles with improved amorphous stability compared to the individual amorphous drugs.

Developing ciprofloxacin dry powder for inhalation: A story of challenges and rational design in the treatment of cystic fibrosis lung infection.

Cystic fibrosis (CF) is an inherited multisystem disease affecting the lung which leads to a progressive decline in lung function as a result of malfunctioning mucociliary clearance and subsequent chronic bacterial infections. Pseudomonas aeruginosa is the predominant cause of lung infection in CF patients and is associated with significant morbidity and mortality. Thus, antibiotic therapy remains the cornerstone of the treatment of CF.

Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan.

Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated.

Chitosan-Coated PLGA Nanoparticles Encapsulating Triamcinolone Acetonide as a Potential Candidate for Sustained Ocular Drug Delivery.

The current treatment for the acquired retinal vasculopathies involves lifelong repeated intravitreal injections of either anti-vascular endothelial growth factor (VEGF) therapy or modulation of inflammation with steroids. Consequently, any treatment modification that decreases this treatment burden for patients and doctors alike would be a welcome intervention. To that end, this research aims to develop a topically applied nanoparticulate system encapsulating a corticosteroid for extended drug release.

Innovative Drying Technologies for Biopharmaceuticals.

In the past two decades, biopharmaceuticals have been a breakthrough in improving the quality of lives of patients with various cancers, autoimmune, genetic disorders etc. With the growing demand of biopharmaceuticals, the need for reducing manufacturing costs is essential without compromising on the safety, quality, and efficacy of products. Batch Freeze-drying is the primary commercial means of manufacturing solid biopharmaceuticals.

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease.

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition.