•A battery-less drug delivery patch capable of controlled release was developed.•Drug release was achieved via soft magnetic actuation.•Device performance was experimentally assessed.•The device ...could pierce the stratum corneum and inject into excised human skin.
This paper presents a magnetic polymer-driven transdermal drug delivery system. Transdermal drug delivery has several advantages over oral and hypodermic administration, including painless delivery and avoiding first-pass metabolism. In this study, magnetic polymer composites (MPCs) and inductive sensing principles were utilized as the key actuator and sensor technologies to enable controlled drug release through a single hollow microneedle. The proposed system is capable of drug dispensing and dosage sensing, without the need for on-board electronics or batteries. Through experimental testing, the battery-less device demonstrated controllable zero-order and pulsatile drug release profiles, and was able to pierce and inject solution into excised human skin. This novel wireless pumping system provides the capability to control the volume dispensed for transdermal delivery in a compact, wearable form factor.
Safe and efficacious modalities of perioperative analgesia are essential for enhanced recovery after surgery. Truncal nerve blocks are one potential adjunct for analgesia of the abdominal wall, and ...in recent years their popularity has increased. Transversus abdominis plane block (TAPB) and rectus sheath block (RSB) have been shown to reduce morphine consumption and improve pain relief after abdominal surgery. These blocks typically require large volumes of local anaesthetic (LA). We aimed to synthesize studies evaluating systemic concentrations of LA after perioperative TAP and RSB to enhance our understanding of systemic LA absorption and the risk of systemic toxicity.
An independent literature review was performed in accordance with the methods outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An electronic search of four databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and PubMed) was conducted. Primary articles measuring systemic concentrations of LA after single-shot bolus TAPB or RSB were included.
Fifteen studies met the inclusion criteria. Rapid systemic LA absorption was observed in all studies. Of a total of 381 patients, mean peak concentrations of LA exceeded toxic thresholds in 33 patients, of whom three reported mild adverse effects. The addition of epinephrine reduced systemic absorption of LA. No instances of seizure or cardiac instability were observed.
Local anaesthetic in TAPB and RSB can lead to detectable systemic concentrations that exceed commonly accepted thresholds of LA systemic toxicity. Our study highlights that these techniques are relatively safe with regard to LA systemic toxicity.
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Corticosteroids such as dexamethasone are first line ophthalmic treatment for non-infectious posterior uveitis. Corticosteroids are often administered via intravitreal injection to ...treat this condition with frequent injections associated with poor treatment adherence and complications such as endophthalmitis. Current ocular implants provide sustained corticosteroid release at predetermined rates and lack the ability for dose individualisation. This study describes the successful fabrication of electrically responsive macroporous polypyrrole (PPy) thin films, and their subsequent application to triggered dexamethasone release. Colloidal crystal films composed of 370nm polymethylmethacrylate colloids were first deposited on ITO coated glass substrates, and subsequently used as sacrificial templates for the fabrication of high surface area, 3-dimensionally ordered macroporous PPy inverse opal (PPy IO) thin films. SEM, UV–Vis reflectance and cyclic voltammetry measurements established that the redox state of the PPy IO films could be controlled via electrical stimulation, which in turn influences both porosity and optical properties of the films. Incorporation of the anti-inflammatory corticosteroid, dexamethasone phosphate (DexP), in the PPy IO films during their fabrication resulted in an effective delivery platform for triggered DexP release. A sustained release profile was observed for the PPy IO–DexP films, bursts of release could be triggered by electrical stimulation. The amount of DexP released from the PPy IO–DexP films was significantly higher than that released from the conventional non-porous PPy–DexP films of comparable mass. Results suggest that electrically responsive PPy IO structures are highly suitable for on-demand drug delivery applications. This technology may enable physicians to fine-tune the required dose according to disease state and patients’ needs to enhance the safety and efficacy of corticosteroid treatment.
Summary
Retinal diseases are currently treated by frequent injections of a drug‐containing solution into the eye, an unpleasant procedure that may lead to complications and low treatment adherence. ...This has been partially addressed by developing implants that once sutured into the sclera or injected into the vitreous can release drug over months to years. However, once these implants are in place, drug release rates cannot be altered based on individual patient needs. Our research within the Buchanan Ocular Therapeutics Unit aims to develop stimuli‐responsive implants that are able to slowly release drug over time, while also allowing for tuneable top‐up dosing based on the disease progression. One such implant is based on porous conducting polymers using an anionic drug as the dopant. While baseline drug release is achieved by diffusion, further drug bursts can be activated by application of a small electrical signal. Two other systems are based on photo‐sensitive polymers that can be cured or activated once injected into the vitreous by shining light through the cornea. This presentation will cover the preparation and evaluation of these stimuli‐responsive systems including in vitro release data.
CONTEXT: Vitamin D is purported to offer wide ranging and numerous health benefits leading to increased interest from manufacturers of medicines and dietary supplements. Elderly patients frequently ...require vitamin D supplementation due to reduced sun exposure and dietary intake. There are ever increasing numbers of vitamin D formulations in the global market. However, due to a lack of regulatory restrictions for some of these products the quality of these dosage forms can be of some concern. OBJECTIVES: To study vitamin D formulations available in the global market and evaluate physic-chemical properties of selected formulations from the New Zealand market. METHOD: The first component of this study consisted of a search for different vitamin D formulations available in selected countries. The second component of the study involved assaying selected vitamin D formulations available in New Zealand. Vitamin D was extracted from capsule, tablet and emulsion formulations and quantified using a validated High Performance Liquid Chromatography (HPLC) method. RESULTS: Of the 14 analysed formulations, only 60% were within 100+10 % of the label claim. The two registered, prescription formulations available exhibited vitamin D levels of 90+4% and 97±2% of the labeled amount, while non-registered, non-prescription dietary supplements had vitamin D levels ranging from 8±2% to 201±29% of the labeled amount. CONCLUSIONS: Dietary supplements do not require strict regulation and showed a large variation in the percentage label claim of vitamin D. Prescription formulations which are more strictly regulated gave content values within standard acceptance ranges. Vitamin D has proven health benefits and also the potential to cause harm, therefore there is a need for tougher regulations of dietary supplements to ensure acceptable quality.
Sequential treatment with paclitaxel (PTXL) and gemcitabine (GEM) is considered clinically beneficial for non-small-cell lung cancer. This study aimed to investigate the effectiveness of a ...nano-system capable of sequential release of PTXL and GEM within cancer cells.
PTXL-ss-poly(6-
-methacryloyl-d-galactopyranose)-GEM (PTXL-ss-PMAGP-GEM) was designed by conjugating PMAGP with PTXL via disulfide bonds (-ss-), while GEM via succinic anhydride (PTXL:GEM=1:3). An amphiphilic block copolymer N-acetyl-d-glucosamine(NAG)-poly(styrene-alt-maleic anhydride)
-b-polystyrene
acted as a targeting moiety and emulsifier in formation of nanostructures (NLCs).
The PTXL-ss-PMAGP-GEM/NAG NLCs (119.6 nm) provided a sequential in vitro release of, first PTXL (redox-triggered), then GEM (pH-triggered). The redox- and pH-sensitive NLCs readily distributed homogenously in the cytoplasm. NAG augmented the uptake of NLCs by the cancer cells and tumor accumulation. PTXL-ss-PMAGP-GEM/NAG NLCs exhibited synergistic cytotoxicity in vitro and strongest antitumor effects in tumor-bearing mice compared to NLCs lacking pH/redox sensitivities or free drug combination.
This study demonstrated the abilities of PTXL-ss-PMAGP-GEM/NAG NLCs to achieve synergistic antitumor effect by targeted intracellularly sequential drug release.
Sustained lidocaine release via a thermoresponsive poloxamer-based in situ gelling system has the potential to alleviate pain following knee arthroplasty. A previously developed formulation showed a ...promising drug release profile in synthetic phosphate-buffered saline (PBS). To support the translation of this formulation, ex vivo characterisation was warranted. This study therefore aimed (1) to modify the previously developed formulation to reduce the burst release, (2) to compare the release behaviour into ex vivo human intra-articular fluid (IAF) and PBS and (3) to determine the formulation spread in an ex vivo human knee using magnetic resonance imaging (MRI). All formulations provided sustained release out to 72 h; polyvinyl pyrrolidone was the most effective additive yielding a small yet significant decrease (
p
< 0.05) in the burst release. Release of lidocaine from the formulation occurred significantly faster into IAF compared to PBS (1.4 times greater release in the first 24 h), correlating with faster rates of gel erosion in IAF. Injection was easily achieved through a 21-gauge (G) needle into the synovial space of a human cadaveric knee, and MRI scans revealed effective spreading of the formulation throughout the joint cavity. The pattern of spread is promising for the drug to reach the widespread nerve endings in the joint capsule; the effect of this spread on release in an in vivo setting will be the subject of future studies. The demonstrated properties indicate that the in situ gelling formulation has the potential to be used clinically to treat post-operative pain following knee arthroplasty.
Patients undergoing arthroplasty require appropriate postsurgical pain relief. Analgesia is typically achieved through bolus doses of short-acting local anesthetics and with oral analgesics such as ...opiates, which are associated with systemic side effects. By formulating an injectable thermosensitive gelling system containing lidocaine, sustained and local delivery can be achieved following a single administration.
Poloxamer-based thermosensitive gelling formulations were prepared. Altering the weight ratios of poloxamers affected the sol-to-gel transition temperature, mechanical and rheological properties and in vitro drug release. Desirable formulations gelled between 28 and 33°C providing sustained release of lidocaine over 48 h.
Thermosensitive gelling systems are promising for sustained drug release following patient administration and may be beneficial in addressing postoperative pain.
Age-related macular degeneration (AMD) and diabetic macular edema (DME) are common causes of blindness in people aged over 55 years. Current treatment involves frequent intravitreal administration of ...corticosteroids such as dexamethasone. The aim of this research was to formulate an electrically controlled delivery system for dexamethasone. Polypyrrole (PPy) was polymerized with dexamethasone sodium phosphate (Dex-P) through two approaches. Firstly, conventional films (CFs) of PPy were electropolymerized by applying a constant current density of 2 mA/cm
2
for 4 min. Secondly, for the first time, we report drug-loaded ethanol-washed films (EWFs). EWFs were prepared in the same manner as CFs, except ethanol washing steps were introduced in the middle and at the end of PPy electropolymerization. The ethanol washing removed unbound PPy oligomers resulting in the formation of smooth surfaces with two distinct layers when viewed in cross-section. The EWFs showed superior electrochemical activity compared to CFs. Sustained release was observed from both CFs and EWFs with bursts of release triggered by electrical stimulation. The EWFs were initially more responsive to the electrical trigger, offering future opportunities to fine tune release. The cytotoxicity of aqueous extracts collected from both films was evaluated on human adult retinal pigment epithelium (ARPE-19) cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with negligible toxicity observed. The results suggest PPy-Dex-P films are highly suitable for the development of electro-responsive implants for the treatment of AMD and DME.
An understanding of biological fluids at the site of administration is important to predict the fate of drug delivery systems in vivo. Little is known about peritoneal fluid; therefore, we have ...investigated this biological fluid and compared it to phosphate-buffered saline, a synthetic media commonly used for in vitro evaluation of intraperitoneal drug delivery systems. Human peritoneal fluid samples were analysed for electrolyte, protein and lipid levels. In addition, physicochemical properties were measured alongside rheological parameters. Significant inter-patient variations were observed with regard to pH (
p
< 0.001), buffer capacity (
p
< 0.05), osmolality (
p
< 0.001) and surface tension (
p
< 0.05). All the investigated physicochemical properties of peritoneal fluid differed from phosphate-buffered saline (
p
< 0.001). Rheological examination of peritoneal fluid demonstrated non-Newtonian shear thinning behaviour and predominantly exhibited the characteristics of an entangled network. Inter-patient and inter-day variability in the viscosity of peritoneal fluid was observed. The solubility of the local anaesthetic lidocaine in peritoneal fluid was significantly higher (
p
< 0.05) when compared to phosphate-buffered saline. Interestingly, the dissolution rate of lidocaine was not significantly different between the synthetic and biological media. Importantly, and with relevance to intraperitoneal drug delivery systems, the sustained release of lidocaine from a thermosensitive gel formulation occurred at a significantly faster rate into peritoneal fluid. Collectively, these data demonstrate the variation between commonly used synthetic media and human peritoneal fluid. The differences in drug release rates observed illustrate the need for bio-relevant media, which ultimately would improve in vitro-in vivo correlation.
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