Hollow microneedles for ocular drug delivery.

Microneedles (MNs) are micron-sized needles, typically <2 mm in length, arranged either as an array or as single needle. These MNs offer a minimally invasive approach to ocular drug delivery due to their micron size (reducing tissue damage compared to that of hypodermic needles) and overcoming significant barriers in drug administration. While various types of MNs have been extensively researched, significant progress has been made in the use of hollow MNs (HMNs) for ocular drug delivery, specifically through suprachoroidal injections. The suprachoroidal space, situated between the sclera and choroid, has been targeted using optical coherence tomography-guided injections of HMNs for the treatment of uveitis. Unlike other MNs, HMNs can deliver larger volumes of formulations to the eye. This review primarily focuses on the use of HMNs in ocular drug delivery and explores their ocular anatomy and the distribution of formulations following potential HMN administration routes. Additionally, this review focuses on the influence of formulation characteristics (e.g., solution viscosity, particle size), HMN properties (e.g., bore or lumen diameter, MN length), and routes of administration (e.g., periocular transscleral, suprachoroidal, intravitreal) on the ocular distribution of drugs. Overall, this paper highlights the distinctive properties of HMNs, which make them a promising technology for improving drug delivery efficiency, precision, and patient outcomes in the treatment of ocular diseases.

Microneedles for advanced ocular drug delivery.

In the field of ocular drug delivery, topical delivery remains the most common treatment option for managing anterior segment diseases, whileintraocular injectionsare the current gold standard treatment option for treating posterior segment diseases. Nonetheless, topical eye drops are associated with low bioavailability (<5%), and theintravitreal administration procedure is highly invasive, yielding poor patient acceptability. In both cases, frequent administration is currently required. As a result, there is a clear unmet need for sustained drug delivery to the eye, particularly in a manner that can be localised. Microneedles, which are patches containing an array of micron-scale needles (<1 mm), have the potential to meet this need. These platforms can enable localised drug delivery to the eye while enhancing penetration of drug molecules through key ocular barriers, thereby improving overall therapeutic outcomes. Moreover, the minimally invasive manner in which microneedles are applied could provide significant advantages over traditional intravitreal injections regarding patient acceptability. Considering the benefitsofthis novel ocular delivery system, this review provides an in-depth overviewofthe microneedle systems for ocular drug delivery, including the types of microneedles used and therapeutics delivered. Notably, we outline and discuss the current challenges associated with the clinical translation of these platforms and offer opinions on factors which should be considered to improve such transition from lab to clinic.

Solid implantable devices for sustained drug delivery.

Implantable drug delivery systems (IDDS) are an attractive alternative to conventional drug administration routes. Oral and injectable drug administration are the most common routes for drug delivery providing peaks of drug concentrations in blood after administration followed by concentration decay after a few hours. Therefore, constant drug administration is required to keep drug levels within the therapeutic window of the drug. Moreover, oral drug delivery presents alternative challenges due to drug degradation within the gastrointestinal tract or first pass metabolism. IDDS can be used to provide sustained drug delivery for prolonged periods of time. The use of this type of systems is especially interesting for the treatment of chronic conditions where patient adherence to conventional treatments can be challenging. These systems are normally used for systemic drug delivery. However, IDDS can be used for localised administration to maximise the amount of drug delivered within the active site while reducing systemic exposure. This review will cover current applications of IDDS focusing on the materials used to prepare this type of systems and the main therapeutic areas of application.

3D bioprinted scaffolds for diabetic wound-healing applications.

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU.

Vitreous Humor: Composition, Characteristics and Implication on Intravitreal Drug Delivery.

Purpose: Intravitreal administration of drug molecules is one of the most common routes for treating posterior segment eye diseases. However, the properties of vitreous humour changes with the time. A number of ocular complications such as liquefaction of the vitreous humour, solidification of the vitreous humour in the central vitreous cavity and detachment of the limiting membrane due to the shrinking of vitreous humour are some of the factors that can drastically affect the efficacy of therapeutics delivered via intravitreal route. Although significant research has been conducted for studying the properties of vitreous humour and its changes during the ageing process, there have been limited work to understand the effect of these changes on therapeutic efficacy of intravitreal drug delivery systems. Therefore, in this review we discussed both the coomposition and characteristics of the vitreous humour, and their subsequent influence on intravitreal drug delivery.Methods: Articles were searched on Scopus, PubMed and Web of Science up to March 2022.Results: In this review, we discussed the biological composition and biomechanical properties of vitreous humour, methods to study the properties of vitreous humour and the changes in these properties and their relevance in ocular drug delivery field, with the aim to provide a useful insight into these aspects which can aid the process of development of novel intravitreal drug delivery systems.Conclusions: The composition and characteristics of the vitreous humour, and how these change during natural aging processes, directly influence intravitreal drug delivery. This review therefore highlights the importance of understanding the properties of the vitreous and identifies the need to achieve greater understanding of how changing properties of the vitreous affect the therapeutic efficacy of drugs administered for the treatment of posterior eye diseases.

Epidemiology of Ocular Manifestations in Autoimmune Disease.

The global prevalence of autoimmune diseases is increasing. As a result, ocular complications, ranging from minor symptoms to sight-threatening scenarios, associated with autoimmune diseases have also risen. These ocular manifestations can result from the disease itself or treatments used to combat the primary autoimmune disease. This review provides detailed insights into the epidemiological factors affecting the increasing prevalence of ocular complications associated with several autoimmune disorders.

3D scaffolds in the treatment of diabetic foot ulcers: New trends vs conventional approaches.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, affecting roughly 25% of diabetic patients and resulting in lower limb amputation in over 70% of known cases. In addition to the devastating physiological consequences of DFU and its impact on patient quality of life, DFU has significant clinical and economic implications. Various traditional therapies are implemented to effectively treat DFU. However, emerging technologies such as bioprinting and electrospinning, present an exciting opportunity to improve current treatment strategies through the development of 3D scaffolds, by overcoming the limitations of current wound healing strategies. This review provides a summary on (i) current prevention and treatment strategies available for DFU; (ii) methods of fabrication of 3D scaffolds relevant for this condition; (iii) suitable materials and commonly used molecules for the treatment of DFU; and (iv) future directions offered by emerging technologies.

The single-leg vertical hop provides unique asymmetry information in individuals after anterior cruciate ligament reconstruction.

BACKGROUND: Traditional testing to identify asymmetries after anterior cruciate ligament reconstruction include four similar horizontal hopping tests. The purpose of this study was to determine whether a single-leg vertical hopping test can identify performance and biomechanical asymmetries, and whether performance asymmetries provide unique information compared to traditional tests. METHODS: Twelve women with history of anterior cruciate ligament reconstruction [age: 21.1 years (SD 3.2), height: 165.8 cm (SD 6.0), mass: 68.3 kg (SD 8.8)] completed traditional horizontal hop testing. Participants also performed a single-leg vertical hop for maximal height while instrumented for three-dimensional motion analysis. Paired t-tests were performed to identify side-to-side differences in performance variables and Spearman's rank correlations were performed of limb symmetry indices to identify whether the single-leg vertical hop test provides unique information. Repeated measures MANOVAs were performed to identify single-leg vertical hop biomechanical asymmetries. FINDINGS: Participants exhibited significant side-to-side performance differences during the single-leg vertical hop [mean difference = 0.02 m (SD 0.03), P = .04]. Only weak to moderate relationships were identified between limb symmetry indices of the single-leg vertical hop and other horizontal hopping tests. The vertical hop elicited significant asymmetries of joint kinematics (P = .04) and angular impulse (P = .04). Specifically, the involved limb showed lower peak ankle dorsiflexion (P = .004) and knee abduction (P = .02) angles, lower sagittal plane impulse at the knee (P = .02) and greater sagittal plane impulse at the hip (P = .03). INTERPRETATION: The single-leg vertical hop can identify performance and biomechanical asymmetries in individuals after anterior cruciate ligament reconstruction, potentially providing complementary information to standard horizontal hopping tests.

A quality assessment of respiratory auscultation material on YouTube.

YouTube contains a large volume of medical educational material. This study assessed the quality of respiratory auscultation videos contained in YouTube. Videos were searched for using the terms 'breath sounds', 'respiratory sounds', 'respiratory auscultation' and/or 'lung sounds'. In total, 6,022 videos were located, 36 of which were considered suitable for scoring for video accuracy, comprehensiveness and quality. The average score was 3.32/6 (55.3% ± 1.30). Video score correlated with time-adjusted YouTube metadata: hits per day (0.496, p=0.002) and likes per day (0.534, p=0.001). Video score also correlated with the first search page on which the video was located in the 'breath sounds' and 'lung sounds' searches (-0.571, p=0.001; -0.445, p=0.014, respectively). The quality of videos was variable. Correlation between video score and some metadata values suggests that there is value for their use in judging video quality. However, the large number of videos found and inability to filter these results quickly makes locating educational content difficult.

Effect of body position on foot and ankle volume in healthy subjects.

Physical therapy treatments for and evaluation of lower limb swelling are usually performed in supine lying position. However, the limb is usually treated or assessed in the dependent position, i.e. sitting or standing. The purpose of this study was to determine the possible confounding effect of subject positioning on foot and ankle volume. Sixty healthy individuals were randomly positioned into motionless standing, sitting or supine lying for 30 min. Volumetric measurements of the dominant leg were taken with a foot and ankle volumeter before and after 30 min of positioning. A significant difference between the three groups for foot and ankle volume change (F(2,53) = 35.41, P<0.001) was found. A post-hoc Tukey HSD test revealed that the difference was statistically significant between sitting and standing as well as supine lying and standing (P<0.001). No statistical significance was found between sitting and supine lying (P = 0.90). Standing caused the greatest increase in foot and ankle volume followed by sitting then supine lying. The results indicate that treating or assessing a limb with the subject in a sitting position would not be significantly different from a subject who is positioned in supine lying. However, it is not known whether the height and the distance from the heart to the feet were comparable between the groups, and so it is recommended that, where possible, treatment and assessment of lower leg swelling should be undertaken with the leg in a non-dependent position and definitely not in standing.