Rachel Yoon Kyung Chang

• PhD
• PostDoc Position at The University of Sydney

Phase contrast x-ray imaging (PCXI) provides high-contrast images of weakly-attenuating structures like the lungs. PCXI, when paired with 4D X-ray Velocimetry (XV), can measure regional lung function and non-invasively assess the efficacy of emerging therapeutics. Bacteriophage therapy is an emerging antimicrobial treatment option for lung diseases...

Phase contrast x-ray imaging (PCXI) provides high-contrast images of weakly-attenuating structures like the lungs. PCXI, when paired with 4D X-ray Velocimetry (XV), can measure regional lung function and non-invasively assess the efficacy of emerging therapeutics. Bacteriophage therapy is an emerging antimicrobial treatment option for lung diseases...

Antimicrobial peptides and proteins (APPs) are gaining attraction as powerful agents against multidrug-resistant bacteria. The inhalation delivery of APPs has emerged as a potent tool for treating respiratory infections, given the ability to achieve high local drug concentrations in the lungs and minimizing systemic exposure. This chapter reviews r...

Dry powder inhalers (DPIs) can be used with a wide range of drugs such as small molecules and biologics and offer several advantages for inhaled therapy. Early DPI products were intended to treat asthma and lung chronic inflammatory disease by administering low-dose, high-potency drugs blended with lactose carrier particles. The use of lactose blen...

Dry powder inhalation formulations have become increasingly popular for local and systemic delivery of small molecules and biotherapeutics. Powder formulations provide distinct advantages over liquid formulations such as elimination of cold chain due to room temperature stability, improved portability, and the potential for increasing patient adher...

Bacteriophage (phage) therapy is a promising treatment strategy to combat antibiotic-resistant bacteria. Clinical reports from a century ago, as well as recent reports have revealed safety and efficacy of phage therapy for bacterial wound infections. However, the conventional liquid phage formulation and delivery platforms reported lack of dose con...

Antibiotic therapy has become increasingly ineffective against bacterial infections due to the rise of resistance. In particular, ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have caused life-threatening infections in humans and repre...

Infections caused by multidrug-resistant (MDR) bacteria have highlighted the importance of the development of new antimicrobial agents. While bacteriophages (phages) are widely studied as alternative agents to antibiotics, combined treatments using phages and antibiotics have exhibited Phage-Antibiotic Synergy (PAS), in which antibiotics promote ph...

Although inhalation powder aerosols of antibiotics have been used to treat respiratory infections caused by Pseudomonas aeruginosa, biofilms are difficult to clear. Ciprofloxacin and D-amino acids (D-Met, D-Trp and D-Phe) were shown to facilitate P. aeruginosa biofilm removal. Spray dried powders for inhalation tend to be amorphous, hence unstable...

Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic con...

Objectives Inhaled phage therapy has been revisited as a potential treatment option for respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa; however, there is a distinct gap in understanding the dose-response effect. The aim of this study was to investigate the dose-response effect of Pseudomonas-targeting phage PEV31...

Background: Respiratory infections are increasingly difficult to treat due to the emergence of multidrug-resistant bacteria. Rediscovery and implementation of inhaled bacteriophage (phage) therapy as a standalone or supplement to antibiotic therapy is becoming recognized as a promising solution to combating respiratory infections caused by these su...

Antimicrobial peptides and proteins (APPs) are becoming increasingly important in targeting multidrug-resistant (MDR) bacteria. APPs is a rapidly emerging area with novel molecules being produced and further optimised to enhance antimicrobial efficacy, while overcoming issues associated with biologics such as potential toxicity and low bioavailabil...

ABSTRACT Intestinal Pseudomonas aeruginosa is highly problematic in immunocompromised patients such as those in intensive care units in hospitals. Phage therapy is an attractive alternative or supplementary therapy to antibiotics as it not only kills multidrug-resistant bacteria, but also minimises the disruption of gut microflora. Solid oral dosag...

Lipid nanoparticles can be optimized for the efficient delivery of mRNA via nebulization.

The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of th...

In vitro-in vivo correlation is the establishment of a predictive relationship between in vitro and in vivo data. In the context of cascade impactor results of orally inhaled pharmaceutical aerosols, this involves the linking of parameters such as the emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter to...

Spray drying is a rapid method for converting a liquid feed into dried particles for inhalation aerosols. Lactose is a major inhalation excipient used in spray-dried (SD) formulations. However, SD powders produced from solutions are usually amorphous hence unstable to moisture. This problem can potentially be minimized by spray drying a suspension...

Hydrogel is an attractive delivery vehicle for phages as it keeps the wound moist, acts as a protective barrier and facilitates wound healing process. The aim of this study was to formulate biologically stable phage hydrogels that enable controlled release of infective phages. Pseudomonas-targeting phages, PEV1 (myovirus) and PEV31 (podovirus) were...

Inhaled drugs are routinely used for the treatment of respiratory-supported patients. To date, pressurized metered dose inhalers and nebulizers are the two platforms routinely employed in the clinical setting. The scarce utilization of the dry powder inhaler (DPI) platform is partly due to the lack of in vivo data that proves optimal delivery and d...

Therapeutic biologics such as genes, peptides, proteins, virus and cells provide clinical benefits and are becoming increasingly important tools in respiratory medicine. Pulmonary delivery of therapeutic biologics enables the potential for safe and effective treatment option for respiratory diseases due to high bioavailability while minimizing abso...

Antibiotic resistance remains as an unresolved global challenge in the health care system, posing serious threats to global health. As an alternative to antibiotics, bacteriophage (phage) therapy is rising as a key to combating antibiotic-resistant bacterial infections. In order to deliver a phage to the site of infection, hydrogels have been formu...

Phage cocktail broadens the host range compared with a single phage and minimizes the development of phage-resistant bacteria thereby promoting the long-term usefulness of inhaled phage therapy. In this study, we produced a phage cocktail powder by spray drying three Pseudomonas phages PEV2 (podovirus), PEV1 and PEV20 (both myovirus) with lactose (...

Inhaled bacteriophage (phage) therapy is a potential alternative to conventional antibiotic therapy to combat multidrug-resistant (MDR) Pseudomonas aeruginosa infections. However, pharmacokinetics (PK) and pharmacodynamics (PD) of phages are fundamentally different to antibiotics and the lack of understanding potentially limits optimal dosing. The...

Lactose is widely used as an approved excipient for dry powder inhaler (DPI) products. Spray drying technique is a rapid method for converting a liquid feed into inhalable dried particles. However, spray-dried (SD) lactose powders produced from solutions are mostly amorphous and particularly unstable when exposed to moisture. In the present study,...

Novel inhalable and synergistic combination powder formulations of phage PEV20 and ciprofloxacin were recently developed to treat Pseudomonas aeruginosa respiratory infections. In the present study, we investigated the storage stability of these powders which comprised ciprofloxacin, lactose and L-leucine in mass ratios of 1:1:1 (Formulation A) or...

Combination treatment using bacteriophage and antibiotics is potentially an advanced approach to combatting antimicrobial-resistant bacterial infections. We have recently developed an inhalable powder by co-spray drying Pseudomonas phage PEV20 with ciprofloxacin. The purpose of this study was to assess the in vivo effect of the powder using a neutr...

Background: Hydroxychloroquine (HCQ) is one of the repurposed drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, all the published clinical trials involve oral administration of the drug, although the disease is primarily a respiratory one. Direct inhaled delivery could reduce the side effects associated with oral use...

Novel inhalable and synergistic combination powder formulations of phage PEV20 and ciprofloxacin were recently developed to treat Pseudomonas aeruginosa respiratory infections. In the present study, we investigated the storage stability of these powders which comprised ciprofloxacin, lactose and L-leucine in mass ratios of 1:1:1 (Formulation A) or...

Endolysins are bacteriophage-derived protein molecules highly effective for bacterial killing. Cpl-1 and ClyJ-3 are native and chimeric endolysins, respectively, having antimicrobial activity against Streptococcus pneumoniae which causes lung infections. We conducted the first feasibility study on nebulisation of Cpl-1 and ClyJ-3, with a focus on t...

Introduction Amorphous powder formulations exist in marketed dry powder inhaler (DPI) products and they will continue to increase. However, amorphous powders are inherently unstable and prone to recrystallize with the aerosol performance reduced if not handled properly. Areas covered In this review, we described the occurrence of amorphous materia...

Cough is an adverse effect that may hinder the delivery of drugs into the lungs. Chemical or mechanical stimulants activate the transient receptor potential in some airway afferent nerves (C‐fibres or A‐fibres) to trigger cough. Types of inhaler device and drug, dose, excipients and formulation characteristics, including pH, tonicity, aerosol outpu...

Inhaled bacteriophage (phage) therapy is a potential alternative to conventional antibiotic therapy to combat multidrug-resistant (MDR) Pseudomonas aeruginosa infections. However, pharmacokinetics (PK) and pharmacodynamics (PD) of phages are fundamentally different to antibiotics and the lack of understanding potentially limits optimal dosing. The...

The clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system has significant therapeutic potentials for lung congenital diseases such as cystic fibrosis, as well as other pulmonary disorders like lung cancer and obstructive diseases. Local administration of CRISPR/Cas9 therapeutics through...

Objectives Pandrug-resistant (PDR) Pseudomonas aeruginosa is one of the three top-priority pathogens identified by the WHO and bacteriophages have been investigated as an alternative therapy. However, knowledge on the pharmacokinetics/pharmacodynamics (PK/PD) of phage therapy is sparse, limiting its clinical applications. This study aimed to evalua...

Recent heightened interest in inhaled bacteriophage (phage) therapy for combating antibacterial resistance in pulmonary infections has led to the development of phage powder formulations. Although phages have been successfully bioengineered into inhalable powders with preserved bioactivity, the stabilization mechanism is yet unknown. This paper rep...

The increasing prevalence of multidrug resistant bacteria has warranted the search for new antimicrobial agents as existing antibiotics lose their potency. Among these, bacteriophage therapy, as well as the administration of specific bacteriolysis agents, i.e., lytic enzymes, have emerged as attractive alternatives. Nebulizers offer the possibility...

Wound infections associated with multidrug-resistant (MDR) bacteria are one of the important threats to public health. Bacteriophage (phage) therapy is a promising alternative or supplementary therapeutic approach to conventional antibiotics for combating MDR bacterial infections. In recent years, significant effort has been put into the developmen...

Use of powder phage formulations for the treatment of multidrug resistant pulmonary infections is gaining attention. To achieve therapeutic benefits, it is critical for phages to remain stable in the formulation. Assessment of phage stability relies on plaque assay (bioactivity), which requires powder samples to be reconstituted in liquid. The purp...

Recently we showed that nebulized ciprofloxacin and phage PEV20 in combination had a synergistic bactericidal effect against antibiotic-resistant Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Compared to nebulization, dry powders for inhalation may improve patient handling characteristics and compliance. In the present study,...

Antibiotic resistance in Pseudomonas aeruginosa biofilms necessitates the need for novel antimicrobial therapy with anti-biofilm properties. Bacteriophages (phages) are recognized as an ideal biopharmaceutical for combating antibiotic-resistant bacteria especially when used in combination with antibiotics. However, previous studies primarily focuse...

The aim of this study was to evaluate the storage stability of inhalable phage powders containing lactose and leucine as excipient. As an FDA-approved excipient for inhalation, lactose is preferred over other sugars. PEV phages active against antibiotic-resistant Pseudomonas aeruginosa was spray dried with lactose (55–90%) and leucine (45–10%). Pro...

Background Aerosol delivery through a nasal high flow (NHF) system is attractive for clinicians as it allows for simultaneous administration of oxygen and inhalable drugs. However, delivering a fine particle fraction (FPF, particle wt. fraction < 5.0 μm) of drugs into the lungs has been very challenging, with highest value of only 8%. Here, we aim...

Nebulization is currently used for delivery of antibiotics for respiratory infections. Bacteriophages (or phages) are effective predators of pathogens including Pseudomonas aeruginosa commonly found in the lungs of patients with cystic fibrosis (CF). It is known that phages and antibiotics can potentially show synergistic antimicrobial effect on ba...

s Tobramycin (TOB) and clarithromycin (CLA) can potentially be used synergistically for the treatment of respiratory infections caused by Pseudomonas aeruginosa (P. aeruginosa) in cystic fibrosis (CF) patients. This study aimed to develop a novel combination proliposome formulation (TOB/CLA-CPROLips) containing both hydrophilic TOB and hydrophobic...

A respiratory infection caused by antibiotic-resistant bacteria can be life-threatening. In recent years, there has been tremendous effort put towards therapeutic application of bacteriophages (phages) as an alternative or supplementary treatment option over conventional antibiotics. Phages are natural parasitic viruses of bacteria that can kill th...

Bacteriophage therapy is a promising alternative treatment to antibiotics as it has been documented to be efficacious against multi-drug resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery; however, phage dry powder administration...

Purpose: To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices. Methods: Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalat...

The potential of bacteriophage therapy for the treatment of pulmonary infections caused by antibiotic-resistant bacteria has been well recognised. The purpose of this study was to investigate the effect of excipients on stabilisation and aerosolisation of spray dried powders of morphologically different phages - PEV podovirus and PEV myovirus. Seve...

Brain tissue from Alzheimer disease patients exhibits synaptic degeneration in selected regions. Synaptic dysfunction occurs early in the disease and is a primary pathological target for treatment. The molecular mechanisms underlying this degeneration remain unknown. Quantifying the synaptic proteome in autopsy brain and comparing tissue from Alzhe...

Background: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is recognized to be a primary pathological target for treatment. Synapse degeneration or dysfunction contributes to clinical signs of dementia through altered neuronal communication; the degree of synaptic loss correlates strongly with cognitive impairment. The molecular...