A trilayer microneedle patch for transdermal delivery of the peptide salmon calcitonin for osteoporosis therapy.

Lipid-based nanocarrier systems have multiple advantages, including biocompatibility, biodegradability and drug loading capacity. Combining these findings with the concept of dissolving microneedles (MNs) would aid in the efficient delivery of peptides and improve therapeutic outcomes. Thus, MN-mediated transdermal delivery was explored for the delivery of salmon calcitonin (sCT).

Lymphatic-targeted amphotericin B nanocrystals delivered using microarray patches applied to cutaneous leishmaniasis.

Leishmaniasis, a parasitic disease transmitted by female sandflies, primarily affects impoverished populations in tropical and subtropical regions. Cutaneous leishmaniasis (CL) is the most prevalent form, with over 600,000 new cases annually. Leishmania parasites spread via the lymphatic system, leading to disease progression.

Transdermal delivery of enfuvirtide using dissolving microneedles integrated with novel insertion and removal indicator.

Enfuvirtide, the first HIV fusion inhibitor, exhibits remarkable antiviral efficacy and a favourable safety profile compared with antiretroviral therapy alone. However, its clinical application is constrained by the necessity for subcutaneous administration and the high incidence of injection site reactions (ISRs) in 98 % of patients. This study seeks to overcome these limitations by developing dissolving microneedle array patches (DMAPs), offering a painless and efficient alternative for enfuvirtide delivery.

Bimodal Dissolving Microneedles with Nanoparticle Coating and Encapsulation for Extended Dual-Drug Delivery.

Effective co-delivery of multiple drugs via microneedle (MN) platforms is challenging due to limited loading capacity and the need for sustained release. This study presents a bimodal coated-dissolving microneedle (DMN) patch for extended delivery of diclofenac (DCF) and dexamethasone (DSP) nanoparticles to treat osteoarthritis. The DMN tips are loaded with DCF nanoparticles (3.

Lyophilised reservoirs in combination with hydrogel-forming microarray patches for transdermal delivery of isoniazid and pyridoxine hydrochloride.

Tuberculosis remains a major global health concern, presenting as either active disease or latent infection, the latter carrying a risk of activation, particularly in immunocompromised individuals. Prolonged isoniazid monotherapy is the standard preventive treatment, often supplemented with pyridoxine to mitigate isoniazid-induced pyridoxine depletion, as recommended by the US Centers for Disease Control and Prevention. This present study investigates an alternative transdermal approach using hydrogel-forming microarray patches (MAPs) incorporating lyophilised isoniazid and pyridoxine wafers.

Development of a nano-vaccine for high-grade serous ovarian cancer.

High-Grade Serous Carcinoma (HGSC) is characterised by aggressive malignant tumours and poor prognosis accounting for 75% of ovarian cancer. Conventional treatments often result in relapse, with a need for innovative therapeutic approaches. This study aimed to develop and evaluate a DNA vaccine targeting the preferentially expressed antigen of melanoma, PRAME, a cancer tumour antigen (CTA) overexpressed in HGSC.

Schizophrenia Treatment Based on Sustained Release of Risperidone from Poly(lactic--glycolic) Acid Implantable Microarray Patch.

Schizophrenia is one of the most severe mental disorders, affecting approximately 24 million people worldwide. Conventional treatments, such as drug-loaded implants and intramuscular injections, have several limitations, including pain during administration and the need for medical professionals to perform the procedure. In this study, a poly(lactic--glycolic) acid (PLGA)-based implantable microneedle patch (IMN) was developed for the transdermal delivery of risperidone (RIS) as a treatment for schizophrenia.

Key considerations for a prostate cancer mRNA vaccine.

Prostate cancer has the second highest cancer mortality rate in the UK in males. Early prostate cancer is typically asymptomatic, with diagnosis at a locally advanced or metastatic stage. In addition, the inherent heterogeneity of prostate cancer tumours differs significantly in terms of genetic, molecular, and histological features.

Biofunctionalisation of porous additively manufactured magnesium-based alloys for Orthopaedic applications: A review.

Magnesium (Mg) alloys have gained significant attention as a desirable choice of biodegradable implant for use in bone repair applications, largely owing to their unique material properties. More recently, Mg and Mg-based alloys have been used as load-bearing metallic scaffolds for bone tissue engineering applications, offering promising opportunities in the field. The mechanical properties and relative density of Mg-based alloys closely approximate those of natural human bone tissue, thereby mitigating the risk of stress-shielding effects.

Strategies for the design of biomimetic cell-penetrating peptides using AI-driven in silico tools for drug delivery.

Cell-penetrating peptides (CPP) have gained rapid attention over the last 25 years; this is attributed to their versatility, customisation, and 'Trojan horse' delivery that evades the immune system. However, the current CPP rational design process is limited, as it requires several rounds of peptide synthesis, prediction and wet-lab validation, which is expensive, time-consuming and requires extensive knowledge in peptide chemistry. Artificial intelligence (AI) has emerged as a promising alternative which can augment the design process, for example by determining physiochemical characteristics, secondary structure, solvent accessibility, disorder and flexibility, as well as predicting in vivo behaviour such as toxicity and peptidase degradation.

Evaluation of physical and chemical modifications to drug reservoirs for stimuli-responsive microneedles.

Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays.

Atorvastatin-Loaded Dissolving Microarray Patches for Long-Acting Microdepot Delivery: Comparison of Nanoparticle and Microparticle Drug Formulations.

The increasing popularity of prolonged-release dosage forms, owing to their ability to provide continuous drug release after administration, has significantly improved patient compliance and overall quality of life. However, achieving prolonged release beyond 24 h frequently requires the use of invasive methods, including injections or implants, which may prove challenging for people suffering from needle phobia. This study introduces atorvastatin (ATR) microparticles (MPs) or nanocrystal (NCs) dissolving microarray patches (D-MAPs) as a noninvasive alternative for intradermal drug delivery over a two-week period for the management of hyperlipidemia.

Enhanced long-acting simvastatin delivery via effervescent powder-carrying hollow microneedles and nanocrystal-loaded microneedles.

Hyperlipidemia and its associated cardiovascular complications are the major causes of mortality and disability worldwide. Simvastatin (SIM) is one of the most commonly prescribed lipid-lowering drugs for the treatment of hyperlipidemia by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. However, the extensive first-pass metabolism leading to low oral bioavailability and frequent daily doses may lead to poor patient compliance and adverse effects caused by plasma fluctuations.

Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies.

Development and Characterization of a Peptide-Bisphosphonate Nanoparticle for the Treatment of Breast Cancer.

In women, breast cancer (BC) is the most common cancer, and despite advancements in diagnosis and treatment, 20-30% of early stage BC patients develop metastatic disease. Metastatic BC is deemed an incurable disease, which accounts for 90% of BC related deaths, with only 26% of metastatic patients reaching a 5 year survival rate. Therefore, there is an unmet need for the prevention or treatment of metastasis in early stage breast cancer patients.

Novel lipid nanovesicle-loaded dissolving microarray patches for fenretinide in breast cancer chemoprevention.

The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faces challenges due to poor solubility and low bioavailability. This study explores the development of dissolving microneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention, aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soya lecithin, water, and polysorbate 80 micelles.

Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive.

Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors.

Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System.

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((Phe)GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated.

Immunotherapy for HPV negative head and neck squamous cell carcinoma.

Head and neck cancer (HNSCC) is the 8th most common cancer in the UK, with incidence increasing due to lifestyle factors such as tobacco and alcohol abuse. HNSCC is an immune-suppressive disease characterised by impaired cytokine secretion and dysregulation of immune infiltrate. As such, immunotherapy is a potential treatment option, with therapeutic cancer vaccination demonstrating the greatest potential.

Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management.

Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. Risperidone (RIS) is a common drug prescribed for the treatment of schizophrenia. RIS is a hydrophobic drug that is typically administered orally or intramuscularly.