Dry Powder Inhaler Formulation of Targeting Infection in Bronchiectasis Maintenance Therapy.

The inhaled delivery of lactic acid bacteria (LAB) probiotics has been demonstrated to exert therapeutic benefits to the lungs due to LAB's immunomodulatory activities. The development of inhaled probiotics formulation, however, is in its nascent stage limited to nebulized LAB. We developed a dry powder inhaler (DPI) formulation of (LGG) intended for bronchiectasis maintenance therapy by spray freeze drying (SFD).

The implementation of chatbot-mediated immediacy for synchronous communication in an online chemistry course.

Unlabelled: Low student engagement and motivation in online classes are well-known issues many universities face, especially with distance education during the COVID-19 pandemic. The online environment makes it even harder for teachers to connect with their students through traditional verbal and nonverbal behaviours, further decreasing engagement. Yet, addressing such problems with 24/7 synchronous communication is overly demanding for faculty.

Amorphous ternary nanoparticle complex of curcumin-chitosan-hypromellose exhibiting built-in solubility enhancement and physical stability of curcumin.

The low aqueous solubility of curcumin (CUR) had greatly limited the clinical efficacy of CUR therapy despite its well-known potent therapeutic activities. Previously, we developed amorphous nanoparticle complex (nanoplex) of CUR and chitosan (CHI) as a solubility enhancement strategy of CUR by electrostatically-driven drug-polyelectrolyte complexation. The CUR-CHI nanoplex, however, (1) lacked a built-in ability to produce prolonged high apparent solubility of CUR in the absence of crystallization-inhibiting agents, and (2) exhibited poor physical stability during long-term storage.

Re-evaluating the presumed superiority of amorphous nanoparticles over amorphous microscale solid dispersion in solubility enhancement of poorly soluble drugs.

The solubility enhancement afforded by amorphous drug nanoparticles was demonstrated in several studies to be superior to the traditional amorphization approach by microscale amorphous solid dispersion (or micro ASD in short). A closer look at these studies, however, revealed that they were performed using a very limited number of poorly-soluble drug models (i.e.

A new bioavailability enhancement strategy of curcumin via self-assembly nano-complexation of curcumin and bovine serum albumin.

Amorphous drug nanoparticles have recently emerged as a superior bioavailability enhancement strategy for poorly soluble drugs in comparison to the conventional microscale amorphous solid dispersions. In particular, amorphous drug nanoparticle complex (or nanoplex) represents an attractive bioavailability enhancement strategy of curcumin (CUR) - a medicinal herb known for its wide-ranging therapeutic activities - attributed to the high payload, cost-effective preparation, and supersaturation generation of the nanoplex. To address the poor colloidal stability of conventional nanoplex formulations, we herein developed a new class of CUR nanoplex by complexation of CUR with bovine serum albumin (BSA).

Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs.

Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing.

Influence of salt type and ionic strength on self-assembly of dextran sulfate-ciprofloxacin nanoplexes.

We evaluated an analytical setup to identify optimal preparation conditions for nanoplex formation of small molecule drugs and polyelectrolytes using ciprofloxacin (CIP) and dextran sulfate (DS) as model compounds. The suitability of isothermal titration calorimetry (ITC) as a screening tool for rational formulation optimization was assessed. Besides ITC, static and dynamic light scattering, zeta potential measurements and scanning electron microscopy were applied to analyze the influence of different salt types and ionic strengths on CIP/DS nanoplex formation.

Preserving the supersaturation generation capability of amorphous drug-polysaccharide nanoparticle complex after freeze drying.

While the supersaturation generation capability of amorphous nanopharmaceuticals (NPs) in their aqueous suspension form has been well established, their supersaturation generation is adversely affected after drying. Herein we investigated the effects of freeze drying on the supersaturation generation capability of a new class of amorphous NPs referred to as drug nanoplex prepared and stabilized by electrostatic complexation of drug molecules with polysaccharides (dextran sulfate). Using ciprofloxacin as the model drug, two types of freeze-drying adjuvants were investigated, i.

Amorphous nanodrugs prepared by complexation with polysaccharides: carrageenan versus dextran sulfate.

Amorphous nanodrugs prepared by electrostatic complexation of drug molecules with oppositely charged polysaccharides represent a promising bioavailability enhancement strategy for poorly-soluble drugs owed to their high supersaturation generation capability and simple preparation. Using ciprofloxacin (CIP) as the model drug, we investigated the effects of using dextran sulfate (DXT) or carrageenan (CGN) on the (1) preparation efficiency, (2) physical characteristics, (3) supersaturation generation, (4) antimicrobial activity, and (5) cytotoxicity of the amorphous drug-polysaccharide nanoparticle complex (nanoplex) produced. Owing to the higher charge density and chain flexibility of DXT, coupled with the greater hydrophobicity of CGN, the CIP-DXT nanoplex exhibited superior preparation efficiency and larger size than the CIP-CGN nanoplex.

Amorphization strategy affects the stability and supersaturation profile of amorphous drug nanoparticles.

Amorphous drug nanoparticles have recently emerged as a promising bioavailability enhancement strategy of poorly soluble drugs attributed to the high supersaturation solubility generated by the amorphous state and fast dissolution afforded by the nanoparticles. Herein we examine the effects of two amorphization strategies in the nanoscale, i.e.

Antibiotic polymeric nanoparticles for biofilm-associated infection therapy.

Polymeric nanoparticles are highly attractive as drug delivery vehicles due to their high structural integrity, stability during storage, ease of preparation and functionalization, and controlled release capability. Similarly, lipid-polymer hybrid nanoparticles, which retain the benefits of polymeric nanoparticles plus the enhanced biocompatibility and prolonged circulation time owed to the lipids, have recently emerged as a superior alternative to polymeric nanoparticles. Drug nanoparticle complex prepared by electrostatic interaction of oppositely charged drug and polyelectrolytes represents another type of polymeric nanoparticle.

Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e.

Controlled release of Lactobacillus rhamnosus biofilm probiotics from alginate-locust bean gum microcapsules.

Chitosan-coated alginate microcapsules containing high-density biofilm Lactobacillus rhamnosus have been previously shown to exhibit higher freeze drying- and thermal-tolerance than their planktonic counterparts. However, their cell release profile remains poor due to the capsules' susceptibility to the gastric environment. Herein the effects of adding locust bean (LB) and xanthan (XT) gums to alginate (AGN) capsules on the stress tolerance and cell release profiles in simulated gastrointestinal fluids are investigated.

Biofilm-like Lactobacillus rhamnosus probiotics encapsulated in alginate and carrageenan microcapsules exhibiting enhanced thermotolerance and freeze-drying resistance.

Microcapsules containing high-density biofilm-like Lactobacillus rhamnosus probiotics, in place of planktonic cells, are developed in order to enhance the cell viability upon exposures to stresses commonly encountered during food lifecycle (i.e., heating, freeze-drying, refrigerated storage, and acid).

Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review.

Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary characteristics of both polymeric nanoparticles and liposomes, particularly in terms of their physical stability and biocompatibility. Significantly, the LPNs have recently been demonstrated to exhibit superior in vivo cellular delivery efficacy compared to that obtained from polymeric nanoparticles and liposomes. Since their inception, the LPNs have advanced significantly in terms of their preparation strategy and scope of applications.

Towards sustainability: new approaches to nano-drug preparation.

The conversion of drugs into drug nanoparticles (nano-drugs) represents a feasible method to enhance bioavailability of otherwise sparingly soluble-drugs. Nano-drugs enhance bioavailability through the improvement of dissolution rate and saturation solubility of drugs, by virtue of their small sizes. Nano-drugs available in the market are usually produced by top-down methods, such as wet milling and high pressure homogenization.

Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.

Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.

Green amorphous nanoplex as a new supersaturating drug delivery system.

The nanoscale formulation of amorphous drugs represents a highly viable supersaturating drug-delivery system for enhancing the bioavailability of poorly soluble drugs. Herein we present a new formulation of a nanoscale amorphous drug in the form of a drug-polyelectrolyte nanoparticle complex (or nanoplex), where the nanoplex is held together by the combination of a drug-polyelectrolyte electrostatic interaction and an interdrug hydrophobic interaction. The nanoplex is prepared by a truly simple, green process that involves the ambient mixing of drug and polyelectrolyte (PE) solutions in the presence of salt.

A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid-polymer hybrid nanoparticles.

Lipid-polymer hybrid nanoparticles - polymeric nanoparticles enveloped by lipid layers - have emerged as a potent therapeutic nano-carrier alternative to liposomes and polymeric nanoparticles. Herein we perform comparative studies of employing spray drying (SD) and spray freeze drying (SFD) to produce inhalable dry-powder form of drug-loaded lipid-polymer hybrid nanoparticles. Poly(lactic-co-glycolic acid), lecithin, and levofloxacin are employed as the polymer, lipid, and drug models, respectively.

Green preparation of antibiotic nanoparticle complex as potential anti-biofilm therapeutics via self-assembly amphiphile-polyelectrolyte complexation with dextran sulfate.

Nanoscale antibiotic delivery has emerged as a promising therapeutic means to treat lung biofilm infection owed to its sputum penetrating ability. Due to the high antibiotic dosage requirement in anti-biofilm therapy, the most suitable formulation for this purpose is the antibiotic nanoparticles themselves, instead of the more extensively studied antibiotic-loaded nano-carriers, which often exhibit low drug loading. The present work details the preparation and characterization of antibiotic nanoparticle complex (or nanoplex) by self-assembly amphiphile-polyelectrolyte complexation process.

Self-assembled amorphous drug-polyelectrolyte nanoparticle complex with enhanced dissolution rate and saturation solubility.

The dissolution rate and solubility of poorly soluble drugs can be enhanced by formulating them into stable amorphous nanoparticle complex (nanoplex). For this purpose, a highly sustainable self-assembly drug-polyelectrolyte complexation process is developed, with ciprofloxacin and dextran sulfate as the drug and polyelectrolyte models, respectively. The nanoplex are prepared by mixing two aqueous salt solutions - one containing the drug and the other containing the oppositely charged polyelectrolyte.

Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles.

Lipid-polymer hybrid nanoparticles are polymeric nanoparticles enveloped by lipid layers that combine the highly biocompatible nature of lipids with the structural integrity afforded by polymeric nanoparticles. Recognizing them as attractive drug delivery vehicles, antibiotics are encapsulated in the present work into hybrid nanoparticles intended for lung biofilm infection therapy. Modified emulsification-solvent-evaporation methods using lipid as surfactant are employed to prepare the hybrid nanoparticles.

Antibacterial efficacy of inhalable antibiotic-encapsulated biodegradable polymeric nanoparticles against E. coli biofilm cells.

Biofilm is a sessile community of bacterial cells enclosed by a self-secreted extracellular polymeric matrix that exhibit a high recalcitrance towards antibiotics. Inhaled antibiotic nanoparticles with a sustained release capability have emerged as one of the most promising anti-biofilm formulations in the fight against respiratory biofilm infections attributed to their ability to penetrate the biofilm sputum. The present work examines the antibacterial efficacies and physical characteristics of different antibiotic-loaded polymeric nanoparticle formulations.

Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: effect of freeze-drying adjuvants.

Inhalable dry-powder aggregates of drug-loaded thermally sensitive poly(caprolactone) (PCL) nanoparticles are produced using spray-freeze-drying (SFD) as the low melting point of PCL prohibits the use of high-temperature spray-drying. The effects of freeze-drying adjuvant formulation on the particle morphology, aerodynamic diameter, aqueous re-dispersibility, flowability, and production yield are examined using mannitol and poly(vinyl alcohol) (PVA) as the adjuvants. The primary role of the adjuvant is to prevent irreversible nanoparticle coalescences during freeze-drying, thereby the nanoparticle aggregates can readily re-disperse into primary nanoparticles in an aqueous environment hence retaining their therapeutic functions.

Antibacterial efficacy of inhalable levofloxacin-loaded polymeric nanoparticles against E. coli biofilm cells: the effect of antibiotic release profile.

Purpose: To investigate the effect of the antibiotic release profiles of levofloxacin-loaded polymeric nanoparticles on their antibacterial efficacy against E. coli biofilm cells.

Methods: Three distinct antibiotic release profiles are produced by encapsulating levofloxacin in PCL and PLGA nanoparticles by nanoprecipitation and emulsification-solvent-evaporation methods.