An investigation into fused filament fabrication for pharmaceutical manufacturing

In a modern world, what is the best way to deliver medicines to the patient? Human beings are an extremely diverse species with many different factors that can influence the behaviour of a drug within the body. Children are a perfect example of such variety. Doses are often prescribed based on body weight, and can vary greatly from infants to adolescents. With current ‘traditional’ manufacture of oral dose pharmaceuticals, generally only a limited number of doses are produced, leading to difficulties with appropriate dosing. The ability to manufacture personalised doses for these patients would be of great benefit both practically and financially, and may even lead to ‘point of care’ manufacture

Recent Development of Electrospinning for Drug Delivery

Several promising techniques have been developed to overcome the poor solubility and/or membrane permeability properties of new drug candidates, including different fiber formation methods. Electrospinning is one of the most commonly used spinning techniques for fiber formation, induced by the high voltage applied to the drug-loaded solution. With modifying the characteristics of the solution and the spinning parameters, the functionality-related properties of the formulated fibers can be finely tuned. The fiber properties (i.e., high specific surface area, porosity, and the possibility of controlling the crystalline–amorphous phase transitions of the loaded drugs) enable the improved rate and extent of solubility, causing a rapid onset of absorption. However, the enhanced molecular mobility of the amorphous drugs embedded into the fibers is also responsible for their physical–chemical instability. This Special Issue will address new developments in the area of electrospun nanofibers for drug delivery and wound healing applications, covering recent advantages and future directions in electrospun fiber formulations and scalability. Moreover, it serves to highlight and capture the contemporary progress in electrospinning techniques, with particular attention to the industrial feasibility of developing pharmaceutical dosage forms. All aspects of small molecule or biologics-loaded fibrous dosage forms, focusing on the processability, structures and functions, and stability issues, are included

Isatin thiosemicarbazone-blended polymer films for biomedical applications : surface morphology, characterisation and preliminary biological assessment

Poly (methyl methacrylate) and polyurethane are polymers currently used for a range of biomedical applications. To modify their surface characteristics, biocompatibility and potentially reduce any related side effects the addition to the polymers of appropriate compounds has been investigated. Isatin thiosemicarbazone derivatives were synthesised and added to poly (methyl methacrylate) and polyurethane solutions before spin coating them on to a silica wafer. The resultant films were characterised with contact angle goniometry and atomic force microscopy. PMMA films produced from tetrahydrofuran solvent displayed honeycombed structures which were highly hydrophobic; however, such changes were not seen for polyurethane surfaces. The cytotoxicity and effect on cell proliferation of polymer surfaces were investigated using PNT2A prostate cells. The isatin-containing polymers were deemed non-toxic at the concentrations used, while cell proliferation studies suggested that the resulting films were supportive of cell growth

A novel PAA derivative with enhanced drug efficacy in pancreatic cancer cell lines.

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1

Recent developments in microfluidic technologies for central nervous system targeted studies

Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.info:eu-repo/semantics/publishedVersio

Liposomal Encapsulation of Amoxicillin via Microfluidics with Subsequent Investigation of the Significance of PEGylated Therapeutics

With an increasing concern of global antimicrobial resistance, the efforts to improve the formulation of a narrowing library of therapeutic antibiotics must be confronted. The liposomal encapsulation of antibiotics using a novel and sustainable microfluidic method has been employed in this study to address this pressing issue, via a targeted, lower-dose medical approach. The study focusses upon microfluidic parameter optimisation, formulation stability, cytotoxicity, and future applications. Particle sizes of circa. 130 nm, with viable short-term (28-day) physical stability were obtained, using two different non-cytotoxic liposomal formulations, both of which displayed suitable antibacterial efficacy. The microfluidic method allowed for high encapsulation efficiencies (≈77 %) and the subsequent in vitro release profile suggested high limits of antibiotic dissociation from the nanovessels, achieving 90% release within 72 h. In addition to the experimental data, the growing use of poly(ethylene) glycol (PEG) within lipid-based formulations is discussed in relation to anti-PEG antibodies, highlighting the key pharmacological differences between PEGylated and non-PEGylated formulations and their respective advantages and drawbacks. It's surmised that in the case of the formulations used in this study, the addition of PEG upon the liposomal membrane would still be a beneficial feature to possess owing to beneficial features such as stability, antibiotic efficacy and the capacity to further modify the liposomal membrane.</p

A comparison study of the degradative effects and safety implications of UVC and 405 nm germicidal light sources for endoscope storage

Storage of flexible endoscopes under germicidal ultraviolet (UVC) light has been associated with degradation of device material leading to failure and increased risk to patients. 405 nm germicidal light presents a possible alternative, potentially providing effective bacterial inactivation without material damage. Samples of endoscope material were exposed to UVC and 405 nm germicidal light sources and a broad spectrum light source control. Material properties were monitored using FTIR, AFM, contact angle and confocal microscopy. Significant changes were observed with samples exposed to the UVC source, with variations in FTIR spectra indicative of side chain scission, a decrease in contact angle from 82.6° to 61.4°, an increase in average surface roughness from 2.34 nm to 68.7 nm and visible cracking of the surface. In contrast samples exposed to the 405 nm light source showed little to no changes, with any variations being comparable to those seen on samples exposed to the broad spectrum control. Bacterial adhesion tests on samples showed an 86.8% increase in Pseudomonas aeruginosa adhesion on UVC exposed samples and no significant increase in adhesion with samples exposed to the other light sources. 405 nm germicidal light therefore potentially represents a safer alternative to UVC light for use in flexible endoscope storage

Thermally reactive N-(2-hydroxypropyl)methacrylamide (HPMA) amphiphiles for drug solubilisation

Thermally active polymers, can respond structurally to temperature changes, making them interesting as potential drug delivery vehicles. Polymers of N-(3-aminopropyl) methacrylamide hydrochloride (APMA) are cationic with primary amine groups in their structure, which have been explored in biomedical applications via post-polymerisation modifications. In this work, we synthesised amphiphilic APMA monomers using hydrophobic pendant groups via conjugation onto their primary amine group. The pendant groups chosen in this study were palmitoyl, dansyl and cholesteryl moieties. The amphiphilic monomers were subsequently copolymerized with N-(2-hydroxypropyl)methacrylamide (HPMA) using varied monomer feed ratios resulting in a thermo-responsive system. The ability of the resultant aggregates in aqueous solution to encapsulate and liberate model drugs (e.g., propofol, griseofulvin and prednisolone) was then determined. Our data showed that the HPMA based formulations were capable of loading the model drug molecules inside their lipophilic core; HPMA-co-(APMA-Dansyl 2%) exhibited the largest drug encapsulation ability. Subsequently, poly(ethylene glycol) (PEG) was incorporated into the intrinsic polymer structure. This resulted in a more rapid drug release profile, whereby 100% of griseofulvin and prednisolone were liberated after only 4 h, which was only 5% and 10% before the PEG inclusion, respectively. Similarly, propofol showed 70% liberation from the polymer aggregate after 24 h, compared with only 30% liberation pre-PEGylation. These studies give an insight into the potential of the HMPA based amphiphiles as thermally responsive cargo carrier/release systems which could be exploited in the delivery of poorly soluble drugs