Tea polyphenols nanoparticles integrated with microneedles multifunctionally boost 5-aminolevulinic acid photodynamic therapy for skin cancer.

5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an emerging therapeutic strategy for skin cancer due to its noninvasiveness and high spatiotemporal selectivity. However, poor skin penetration, poor intratumoral delivery, the instability of aqueous ALA, and the tumor's inherent hypoxia microenvironment are major hurdles hindering the efficacy of ALA-PDT. Herein, we aim to address these challenges by using microneedles (MNs) to assist in delivering nanoparticles based on natural polymeric tea polyphenols (TP NPs) to self-assemble and load ALA (ALA@TP NPs).

Dry powder inhalation containing muco-inert ciprofloxacin and colistin co-loaded liposomes for pulmonary P. Aeruginosa biofilm eradication.

Pseudomonas aeruginosa (PA), a predominant pathogen in lung infections, poses significant challenges due to its biofilm formation, which is the primary cause of chronic and recalcitrant pulmonary infections. Bacteria within these biofilms exhibit heightened resistance to antibiotics compared to their planktonic counterparts, and their secreted toxins exacerbate lung infections. Diverging from traditional antibacterial therapy for biofilm eradication, this study introduces a novel dry powder inhalation containing muco-inert ciprofloxacin and colistin co-encapsulated liposomes (Cipro-Col-Lips) prepared using ultrasonic spray freeze drying (USFD) technique.

Cocrystallization of Gefitinib Potentiate Single-Dose Oral Administration for Lung Tumor Eradication via Unbalancing the DNA Damage/Repair.

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy.

Nanotechnology-Based Drug Delivery Systems to Control Bacterial-Biofilm-Associated Lung Infections.

Airway mucus dysfunction and impaired immunological defenses are hallmarks of several lung diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary diseases, and are mostly causative factors in bacterial-biofilm-associated respiratory tract infections. Bacteria residing within the biofilm architecture pose a complex challenge in clinical settings due to their increased tolerance to currently available antibiotics and host immune responses, resulting in chronic infections with high recalcitrance and high rates of morbidity and mortality. To address these unmet clinical needs, potential anti-biofilm therapeutic strategies are being developed to effectively control bacterial biofilm.

Co-Delivery of Loxoprofen and Tofacitinib by Photothermal Microneedles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is an autoimmune disease of synovial inflammation that affects populations worldwide. Transdermal drug delivery systems for treating RA have increased but remain challenging. We fabricated a dissolving microneedle (MN) system with photothermal (PT) polydopamine (PDA) to co-load the non-steroidal anti-inflammatory drug loxoprofen (Lox) and the Janus kinase inhibitor tofacitinib (Tof), with the aim of co-delivering Lox and Tof directly to the articular cavity, aided by the combination of MN and PT.

Fibroblast activation protein α activatable theranostic pro-photosensitizer for accurate tumor imaging and highly-specific photodynamic therapy.

The development of activatable photosensitizers (aPSs) responding to tumor-specific biomarkers for precision photodynamic therapy (PDT) is urgently required. Due to the unique proteolytic activity and highly restricted distribution of tumor-specific enzymes, enzyme activatable photosensitizers display superior selectivity. Herein, a series of novel Fibroblast Activation Protein α (FAPα) activatable theranostic pro-photosensitizers were designed by conjugating the different -terminal blocked FAPα-sensitive dipeptide substrates with a clinical PS, methylene blue (MB), through a self-immolative linker, which resulting in the annihilation of the photoactivity (fluorescence and phototoxicity).

An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin.

Inhaled antibiotics such as colistin and ciprofloxacin are increasingly used to treat bacterial lung infections in cystic fibrosis patients. In this study, we established and validated a new HPLC-MS/MS method that could simultaneously detect drug concentrations of ciprofloxacin, colistin and ivacaftor in rat plasma, human epithelial cell lysate, cell culture medium, and drug transport media. An aliquot of 200 μL drug-containing rat plasma or cell culture medium was treated with 600 μL of extraction solution (acetonitrile containing 0.

LC-MS/MS method for simultaneous quantification of dexamethasone and tobramycin in rabbit ocular biofluids.

The complexity of Tobradex® ointment formulation (dexamethasone 0.1 wt% and tobramycin 0.3 wt%) and the high cost of pharmacokinetic (PK) studies in human aqueous humor may prevent generic drug companies from moving forward with a Tobradex®-equivalent product development.

Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.

Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus.

Sunitinib malate-loaded biodegradable microspheres for the prevention of corneal neovascularization in rats.

Corneal neovascularization (NV) predisposes patients to compromised corneal transparency and visional acuity. Sunitinib malate (Sunb-malate) targeting against multiple receptor tyrosine kinases, exerts potent antiangiogenesis. However, the rapid clearance of Sunb-malate eye drops administered through topical instillation limits its therapeutic efficacy and poses a challenge for potential patient compliance.

Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery.

Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIPs) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIPs was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2 μm; and >80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI).

Optimization of inhalable liposomal powder formulations and evaluation of their in vitro drug delivery behavior in Calu-3 human lung epithelial cells.

Inhalation therapy has advantages for the treatment of multidrug resistant bacterial lung infections with high drug concentrations at the infection sites in the airways and reduced systemic exposure. We have developed liposomal formulations for pulmonary delivery of synergistic ciprofloxacin (Cipro) and colistin (Col) as the potential candidate for treatment of lung infections caused by multidrug resistant Gram-negative bacteria. This study aims to: (1) further optimize the powder formulation by adding drying stabilizers (polyvinyl pyrrolidone or poloxamer) to protect the liposomes during spray-freeze-drying; (2) evaluate the transport and cellular uptake of drugs in a human lung epithelial Calu-3 cell model.

Inhalable liposomal powder formulations for co-delivery of synergistic ciprofloxacin and colistin against multi-drug resistant gram-negative lung infections.

The aim of this study was to design and characterize dry powder inhaler formulations of ciprofloxacin and colistin co-loaded liposomes prepared by the ultrasonic spray-freeze-drying (USFD) technique. Liposomal formulations and powder production parameters were optimized to achieve optimal characteristics and in-vitro performance such as encapsulation efficiency (EE), particle size, particle distribution index (PDI), fine particle fraction (FPF), emitted dose (ED) and in vitro antibacterial activity. The formulation (F6) with the mannitol (5% w/v) as the internal lyoprotectant and sucrose (5%, w/v), mannitol (10%, w/v) and leucine (5%, w/w) as the external lyoprotectants/aerosolization enhancers showed an optimal rehydrated EE values of ciprofloxacin and colistin (44.

Evaluation of co-delivery of colistin and ciprofloxacin in liposomes using an in vitro human lung epithelial cell model.

Respiratory tract infections caused by multidrug-resistant Gram-negative bacteria are serious burdens to the public. Our previous findings indicated that co-loading of colistin and ciprofloxacin via liposomes improved in vitro antimicrobial activities against multidrug resistant Pseudomonas aeruginosa as compared to the monotherapies. The current study aims to investigate the transport behavior of colistin and ciprofloxacin in liposomes using the in vitro Calu-3 cell monolayer, which is a lung epithelial model cultured under the air-interfaced condition.

Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa.

Purpose: This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa.

Methods: Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated.

Transport Mechanisms of Solid Lipid Nanoparticles across Caco-2 Cell Monolayers and their Related Cytotoxicology.

Solid lipid nanoparticles (SLNs) have been extensively investigated and demonstrated to be a potential nanocarriers for improving oral bioavailability of many drugs. However, the molecular mechanisms related to this discovery are not yet understood. Here, the molecular transport mechanisms of the SLNs crossing simulative intestinal epithelial cell monolayers (Caco-2 cell monolayers) were studied.

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system.

Purpose: Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis.

Methods: The molecular structures of TC-PLGA were validated by (1)H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method.

Transport pathways of solid lipid nanoparticles across Madin-Darby canine kidney epithelial cell monolayer.

An understanding of drug delivery system transport across epithelial cell monolayer is very important for improving the absorption and bioavailability of the drug payload. The mechanisms of epithelial cell monolayer transport for various nanocarriers may differ significantly due to their variable components, surface properties, or diameter. Solid lipid nanoparticles (SLNs), conventionally formed by lipid materials, have gained increasing attention in recent years due to their excellent biocompatibility and high oral bioavailability.

Improved transport and absorption through gastrointestinal tract by PEGylated solid lipid nanoparticles.

The aim of the present study was to evaluate the potential of PEGylated solid lipid nanoparticle (pSLN) as mucus penetrating particles (MPP) for oral delivery across gastrointestinal mucus. The SLN was prepared by an aqueous solvent diffusion method, subsequently modified with PEG2000-stearic acid (PEG2000-SA) as hydrophilic groups. Surface properties, cytotoxicity, cellular uptake, and transport across Caco-2/HT29 coculture cell monolayers, intestinal absorption, and pharmacokinetics of pSLN were studied compared with that of SLN.

Protective effect of polysaccharides on the stability of parenteral emulsions.

The main purpose of this study is to investigate the influence of two polysaccharides (dextran, hydroxyethyl starch) on the stability of parenteral emulsions. All parenteral emulsions were prepared by high-pressure homogenization. The influence of polysaccharides concentration was studied.

Preparation of fenofibrate immediate-release tablets involving wet grinding for improved bioavailability.

Objective: The purpose of this study was to investigate the dissolution and oral bioavailability of an immediate-release tablet involving wet grinding of a poorly water-soluble drug, fenofibrate.

Methods: The milled suspension was prepared using a Basket Dispersing Mill in the presence of a hydrophilic polymer solution and then granulated with common excipients, and compressed into an immediate-release tablet with blank microcrystalline cellulose granules.

Results: Compared with unmilled tablets (56% within 30 minutes), the dissolution of wet-milled tablets (about 98% in 30 minutes) was markedly enhanced.