Nanostructured lipid carriers for enhanced batimastat delivery across the blood-brain barrier: an in vitro study for glioblastoma treatment.

Glioblastoma presents a significant treatment challenge due to the blood-brain barrier (BBB) hindering drug delivery, and the overexpression of matrix metalloproteinases (MMPs), which promotes tumor invasiveness. This study introduces a novel nanostructured lipid carrier (NLC) system designed for the delivery of batimastat, an MMP inhibitor, across the BBB and into the glioblastoma microenvironment. The NLCs were functionalized with epidermal growth factor (EGF) and a transferrin receptor-targeting construct to enhance BBB penetration and entrapment within the tumor microenvironment.

The Printed Path to Healing: Advancing Wound Dressings through Additive Manufacturing.

Wound care challenges healthcare systems worldwide as traditional dressings often fall short in addressing the diverse and complex nature of wound healing. Given conventional treatments limitations, innovative alternatives are urgent. Additive manufacturing (AM) has emerged as a distinct and transformative approach for developing advanced wound dressings, offering unprecedented functionality and customization.

Co-delivery of antioxidants and siRNA-VEGF: promising treatment for age-related macular degeneration.

Current treatments for retinal disorders are anti-angiogenic agents, laser photocoagulation, and photodynamic therapies. These conventional treatments focus on reducing abnormal blood vessel formation in the retina, which, in a low-oxygen environment, can lead to harmful proliferation of endothelial cells. This results in dysfunctional, leaky blood vessels that cause retinal edema, hemorrhage, and vision loss.

Advancing osteosarcoma 3D modeling in vitro for novel tumor microenvironment-targeted therapies development.

Osteosarcoma (OS) represents one of the most common primary bone cancers affecting children and young adults. The available treatments have remained unimproved for the past decades, hampered by the poor knowledge of OS etiology/pathophysiology and the lack of innovative, predictive and biologically relevant in vitro models, that can recapitulate the 3D OS tumor microenvironment (TME). Here, we report the development and characterization of an innovative 3D model of OS, composed of OS tumor cells, immune cells (macrophages) and mesenchymal stem cells (MSCs), that formed a multicellular tissue spheroid (MCTS).

Patient-Derived Melanoma Immune-Tumoroids as a Platform for Precise High throughput Drug Screening.

In vitro models are crucial in cancer research, but they must truthfully mimic in vivo tumors for clinical relevance. The development of unprecedent melanoma quadruple multicellular tumoroids (MCTs) is proposed comprising tumor cells, keratinocytes, fibroblasts, and monocytes that replicate tumor architecture, tumor microenvironment, and secretome behavior. These MCTs of 300 µm in diameter secreted keratin and collagen, showing complexity proportional to their cell combinations.

Exploring Nanocarriers for Boosting Entacapone Bioavailability: A Journey through System Characterization and Assessment of Toxicity and Pharmacological and 2D Permeability Paybacks.

Catechol--methyltransferase inhibitors (iCOMT), such as entacapone, have been successfully employed to treat tremor-related symptoms of Parkinson's disease. However, iCOMT has been associated with a short half-life and poor oral bioavailability. Nanobased drug delivery systems have often been used to overcome this type of setbacks.

Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model.

The oral administration of the glucagon-like peptide-1 analogue, semaglutide, remains a hurdle due to its limited bioavailability. Herein, neonatal Fc receptor (FcRn)-targeted nanoparticles (NPs) were designed to enhance the oral delivery of semaglutide. The nanocarriers were covalently linked to the FcRn-binding peptide FcBP or the affibody molecule Z that specifically binds to the human FcRn (hFcRn) in a pH-dependent manner.

The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery.

Introduction: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low.

A translational framework to DELIVER nanomedicines to the clinic.

Nanomedicines have created a paradigm shift in healthcare. Yet fundamental barriers still exist that prevent or delay the clinical translation of nanomedicines. Critical hurdles inhibiting clinical success include poor understanding of nanomedicines' physicochemical properties, limited exposure in the cell or tissue of interest, poor reproducibility of preclinical outcomes in clinical trials, and biocompatibility concerns.

Bioengineering lipid-based synthetic cells for therapeutic protein delivery.

Synthetic cells (SCs) offer a promising approach for therapeutic protein delivery, combining principles from synthetic biology and drug delivery. Engineered to mimic natural cells, SCs provide biocompatibility and versatility, with precise control over their architecture and composition. Protein production is essential in living cells, and SCs aim to replicate this process using compartmentalized cell-free protein synthesis systems within lipid bilayers.

Freeze-drying cycle optimization of an amorphous solid dispersion of resveratrol.

Resveratrol (RES) has demonstrated advantages as anti-cancer, anti-inflammatory, blood sugar-lowering agent and as cardioprotective agent, among others. Despite RES therapeutic advantages its use in pharmaceutical applications is limited by its low oral bioavailability, mainly due to its poor water solubility. Formulation of poorly water-soluble compound as solid dispersion (SD) converts a crystalline into a more soluble in water amorphous drug.

Chemical engineering of zein with polyethylene glycol and Angiopep-2 to manufacture a brain-targeted docetaxel nanomedicine for glioblastoma treatment.

Glioblastoma (GBM) is the deadliest adult brain cancer. The current standard-of-care chemotherapy using orally administered temozolomide (TMZ) presents poor improvement in patient survival, emphasizing the compelling need for new therapies. A possible chemotherapeutic alternative is docetaxel (DTX), which possesses higher tumoricidal potency against GBM cells.

Orally Delivered Stimulus-Sensitive Nanomedicine to Harness Teduglutide Efficacy in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract (GIT). Glucagon-like peptide-2 (GLP-2) analogs possess high potential in the treatment of IBD by enhancing intestinal repair and attenuating inflammation. Due to the enzymatic degradation and poor intestinal absorption, GLP-2 analogs are administered parenterally, which leads to poor patient compliance.

Neuro-Immunomodulatory Potential of Nanoenabled 4D Bioprinted Microtissue for Cartilage Tissue Engineering.

Cartilage defects trigger post-traumatic inflammation, leading to a catabolic metabolism in chondrocytes and exacerbating cartilage degradation. Current treatments aim to relieve pain but fail to target the inflammatory process underlying osteoarthritis (OA) progression. Here, a human cartilage microtissue (HCM) nanoenabled with ibuprofen-loaded poly(lactic-co-glycolic acid) nanoparticles (ibu-PLGA NPs) is 4D-bioprinted to locally mitigate inflammation and impair nerve sprouting.

GLP-1 Analogue-Loaded Glucose-Responsive Nanoparticles as Allies of Stem Cell Therapies for the Treatment of Type I Diabetes.

Type 1 diabetes (T1D) is characterized by insufficient insulin secretion due to β-cell loss. Despite exogenous insulin administration being a lifesaving treatment, many patients still experience severe glycemic lability. For these patients, a β-cell replacement strategy through pancreas or pancreatic islet transplantation is the most physiological approach.

Self-assembly mucoadhesive beads of κ-carrageenan/sericin for indomethacin oral extended release.

Oral drug administration, especially when composed of mucoadhesive delivery systems, has been a research trend due to increased residence time and contact with the mucosa, potentially increasing drug bioavailability and stability. In this context, this study aimed to develop self-assembly mucoadhesive beads composed of blends of κ-carrageenan and sericin (κ-Car/Ser) loaded with the anti-inflammatory drug indomethacin (IND). We investigated the swelling, adhesion behaviour, and mechanical/physical properties of the beads, assessing their effects on cell viability, safety and permeation characteristics in both 2D and triple-culture model.

Vitamin D loaded into lipid nanoparticles shows insulinotropic effect in INS-1E cells.

Increasing evidence suggests a beneficial role of vitamin D (VitD) supplementation in addressing the widespread VitD deficiency, but currently used VitD3 formulations present low bioavailability and toxicity constrains. Hence, poly(L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), solid-lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were investigated to circumvent these issues. PLGA NPs prepared by emulsification or nanoprecipitation presented 74 or 200 nm, and association efficiency (AE) of 68 % and 17 %, respectively, and a rapid burst release of VitD3.

Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy.

Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic--glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties.

Bridging the gap between testing and clinics exploring alternative pre-clinical models in melanoma research.

Melanoma, the deadliest form of skin cancer, poses a significant clinical challenge for the development of effective treatments. Conventional in vivo animal studies have shown limited translational relevance to humans, raising strength to pre-clinical models for melanoma research. This review provides an in-depth analysis of alternative pre-clinical models including in vitro and ex vivo platforms such as reconstructed skin, spheroids, organoids, organotypic models, skin-on-a-chip, and bioprinting.

New insights into nanomedicines for oral delivery of glucagon-like peptide-1 analogs.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that arises when the body cannot respond fully to insulin, leading to impaired glucose tolerance. Currently, the treatment embraces non-pharmacological actions (e.g.

Third-Generation Solid Dispersion Through Lyophilization Enhanced Oral Bioavailability of Resveratrol.

Resveratrol (RES) is a biopharmaceutical classification system (BCS) class II compound with low solubility and high permeability. Several strategies have been explored to overcome the low bioavailability of RES, making the formation of solid dispersions (SDs) one of the most promising. This study aimed at the development of a RES third-generation SD prepared by lyophilization as a strategy to improve RES solubility, dissolution, and oral bioavailability.

A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy.

Cancer presents a high mortality rate due to ineffective treatments and tumour relapse with progression. Cancer vaccines hold tremendous potential due to their capability to eradicate tumour and prevent relapse. In this study, we present a novel glycovaccine for precise targeting and immunotherapy of aggressive solid tumours that overexpress CD44 standard isoform (CD44s) carrying immature Tn and sialyl-Tn (sTn) O-glycans.

Trends in 3D models of inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a set of chronic inflammatory conditions, namely Crohn's disease and ulcerative colitis. Despite all advances in the management of IBD, a definitive cure is not available, largely due to a lack of a holistic understanding of its etiology and pathophysiology. Several in vitro, in vivo, and ex vivo models have been developed over the past few decades in order to abbreviate remaining gaps.