Matrix metalloproteinase responsive hydrogel microplates for programmed killing of invasive tumour cells.

Interactive materials are an emerging class of systems that can offer control over response and adaptivity in polymer structures towards the meso- and macroscale. Here, we use enzyme regulated cleavage of peptide crosslinkers in polymer hydrogels to release a cytotoxic therapeutic nanoparticle with an adaptable mechanism. Hydrogel microplates were formed through polyethylene glycol/peptide photoinitiated thiol-ene chemistry in a soft-lithography process to give square plates of 20 by 20 μm with a height of 10 μm.

Augmented efficacy of nano-formulated docetaxel plus curcumin in orthotopic models of neuroblastoma.

Neuroblastoma is a biologically heterogeneous extracranial tumor, derived from the sympathetic nervous system, that affects most often the pediatric population. Therapeutic strategies relying on aggressive chemotherapy, surgery, radiotherapy, and immunotherapy have a negative outcome in advanced or recurrent disease. Here, spherical polymeric nanomedicines (SPN) are engineered to co-deliver a potent combination therapy, including the cytotoxic docetaxel (DTXL) and the natural wide-spectrum anti-inflammatory curcumin (CURC).

Microfluidic assembly of "Turtle-Like" shaped solid lipid nanoparticles for lysozyme delivery.

After two decades of research in the field of nanomedicine, nanoscale delivery systems for biologicals are becoming clinically relevant tools. Microfluidic-based fabrication processes are replacing conventional techniques based on precipitation, emulsion, and homogenization. Here, the focus is on solid lipid nanoparticles (SLNs) for the encapsulation and delivery of lysozyme (LZ) as a model biologic.

Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis.

Posttraumatic osteoarthritis (PTOA) is mostly treated via corticosteroid administration, and total joint arthroplasty continues to be the sole effective intervention in severe conditions. To assess the therapeutic potential of CCR2 targeting in PTOA, we used biodegradable microplates (µPLs) to achieve a slow and sustained intraarticular release of the CCR2 inhibitor RS504393 into injured knees and followed joint damage during disease progression. RS504393-loaded µPLs (RS-µPLs) were fabricated via a template-replica molding technique.

Shape-specific microfabricated particles for biomedical applications: a review.

The storied history of controlled the release systems has evolved over time; from degradable drug-loaded sutures to monolithic zero-ordered release devices and nano-sized drug delivery formulations. Scientists have tuned the physico-chemical properties of these drug carriers to optimize their performance in biomedical/pharmaceutical applications. In particular, particle drug delivery systems at the micron size regime have been used since the 1980s.

Management of osteoarthritis: From drug molecules to nano/micromedicines.

With the change in lifestyle and aging of the population, osteoarthritis (OA) is emerging as a major medical burden globally. OA is a chronic inflammatory and degenerative disease initially manifesting with joint pain and eventually leading to permanent disability. To date, there are no drugs available for the definitive treatment of osteoarthritis and most therapies have been palliative in nature by alleviating symptoms rather than curing the disease.

Insulin Granule-Loaded MicroPlates for Modulating Blood Glucose Levels in Type-1 Diabetes.

Type-1 diabetes (T1DM) is a chronic metabolic disorder resulting from the autoimmune destruction of β cells. The current standard of care requires multiple, daily injections of insulin and accurate monitoring of blood glucose levels (BGLs); in some cases, this results in diminished patient compliance and increased risk of hypoglycemia. Herein, we engineered hierarchically structured particles comprising a poly(lactic--glycolic) acid (PLGA) prismatic matrix, with a 20 × 20 μm base, encapsulating 200 nm insulin granules.

Boosting nanomedicine performance by conditioning macrophages with methyl palmitate nanoparticles.

Surface PEGylation, biological camouflage, shape and stiffness modulation of nanoparticles as well as liver blockade and macrophage depletion have all improved the blood longevity of nanomedicines. Yet, the mononuclear phagocytic system still recognizes, sequesters, and processes the majority of blood borne particles. Here, the natural fatty acid methyl palmitate is combined with endogenous blood components - albumin - realizing ∼200 nm stable, spherical nanoparticles (MPN) capable of inducing a transient and reversible state of dormancy into macrophages.

Top-Down Fabricated microPlates for Prolonged, Intra-articular Matrix Metalloproteinase 13 siRNA Nanocarrier Delivery to Reduce Post-traumatic Osteoarthritis.

Post-traumatic osteoarthritis (PTOA) associated with joint injury triggers a degenerative cycle of matrix destruction and inflammatory signaling, leading to pain and loss of function. Here, prolonged RNA interference (RNAi) of matrix metalloproteinase 13 (MMP13) is tested as a PTOA disease modifying therapy. MMP13 is upregulated in PTOA and degrades the key cartilage structural protein type II collagen.

Shape-Defined microPlates for the Sustained Intra-articular Release of Dexamethasone in the Management of Overload-Induced Osteoarthritis.

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 μm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (μPLs) are created and intra-articularly deposited for the sustained release of DEX.

Synthesis of Two Methotrexate Prodrugs for Optimizing Drug Loading into Liposomes.

Methotrexate (MTX), a compound originally used as an anticancer drug, has also found applications in a broad variety of autoimmune disorders thanks to its anti-inflammation and immunomodulatory functions. The broad application of MTX is anyway limited by its poor solubility in biological fluids, its poor bioavailability and its toxicity. In addition, encapsulating its original form in nanoformulation is very arduous due to its considerable hydrophobicity.

Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol.

Modulating the Distant Spreading of Patient-Derived Colorectal Cancer Cells via Aspirin and Metformin.

Although screening has reduced mortality rates for colorectal cancer (CRC), about 20% of patients still carry metastases at diagnosis. Postsurgery chemotherapy is toxic and induces drug resistance. Promising alternative strategies rely on repurposing drugs such as aspirin (ASA) and metformin (MET).

Optimizing the Pharmacological Properties of Discoidal Polymeric Nanoconstructs Against Triple-Negative Breast Cancer Cells.

Fine-tuning loading and release of therapeutic and imaging agents associated with polymeric matrices is a fundamental step in the preclinical development of novel nanomedicines. Here, 1,000 × 400 nm Discoidal Polymeric Nanoconstructs (DPNs) were realized via a top-down, template-based fabrication approach, mixing together poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-diacrylate (PEG-DA) chains in a single polymer paste. Two different loading strategies were tested, namely the "direct loading" and the "absorption loading.

Engineering shape-defined PLGA microPlates for the sustained release of anti-inflammatory molecules.

Over the years, nanoparticles, microparticles, implants of poly(D,l-lactide-co-glycolide) (PLGA) have been demonstrated for diverse biomedical applications. Yet, initial burst release and optimal modulation of the release profiles limit their clinical use. Here, shape-defined PLGA microPlates (μPLs) were realized for the sustained release of two anti-inflammatory molecules, the natural polyphenol curcumin (CURC) and the corticosteroid dexamethasone (DEX).

Hierarchical Microplates as Drug Depots with Controlled Geometry, Rigidity, and Therapeutic Efficacy.

A variety of microparticles have been proposed for the sustained and localized delivery of drugs with the objective of increasing therapeutic indexes by circumventing filtering organs and biological barriers. Yet, the geometrical, mechanical, and therapeutic properties of such microparticles cannot be simultaneously and independently tailored during the fabrication process to optimize their performance. In this work, a top-down approach is employed to realize micron-sized polymeric particles, called microplates (μPLs), for the sustained release of therapeutic agents.

Physicochemical characterization of pH-responsive and fusogenic self-assembled non-phospholipid vesicles for a potential multiple targeting therapy.

In order to obtain nanocarriers suitable for the delivery of drugs in the treatment of cancer, pH-responsive nanovesicles capable of facilitating fusion (fusogenic nanovesicles) were synthesized and then their physicochemical characteristics were modified. These nanovesicles were made by combining polysorbates having different physicochemical features with the aim of realizing multiple-targeting nanoformulations suitable for in vitro treatment of cancer cells. Tween21 and Tween80 were self-assembled at different molar concentrations resulting in pH-responsive fusogenic nanovesicles with an average size of less than 150nm, and a narrow size distribution (polydispersity index) value of less than 0.

Acronychiabaueri Analogue Derivative-Loaded Ultradeformable Vesicles: Physicochemical Characterization and Potential Applications.

Elastic and ultradeformable liposomes were synthesized and physicochemically characterized to make suitable topical formulations for delivering the anti-inflammatory and anticancer compound 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid. The average sizes of elastic and ultradeformable liposomes are below 300 nm, while the size distribution and Z-potential are below 0.3 and - 25 mV, respectively.

Microextraction by packed sorbent and HPLC-PDA quantification of multiple anti-inflammatory drugs and fluoroquinolones in human plasma and urine.

We developed and validated an analytical method based on microextraction packed sorbent (MEPS) and high-performance liquid chromatography (HPLC) coupled to photodiode array (PDA) detector to simultaneously quantify multiple nonsteroidal anti-inflammatory drugs (NSAIDs) and fluoroquinolones (FLQs), which may provide as combination several adverse reactions in nephrology and neurology. The linearity range from LOQs (0.1 μg/mL) to 10 μg/mL, and LODs values were 0.

PDE5 Inhibitors-Loaded Nanovesicles: Physico-Chemical Properties and In Vitro Antiproliferative Activity.

Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP). Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase.

HPLC-FLD and spectrofluorometer apparatus: How to best detect fluorescent probe-loaded niosomes in biological samples.

The analytical tools allow the detection of bioactive compounds, diagnostic agents and chemotherapeutics. Recently, new methods have been developed to analyze pharmaceutical samples and ingredients. In this attempt, analytical parameters, e.