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Article ; Online: Pluripotent stem cells as a therapy for type 1 diabetes.

Tuch, Bernard E / Cheng, Iris S / Dang, Hoang Phuc / Chen, Hui / Dargaville, Tim R

Progress in molecular biology and translational science

2023 Volume 199, Page(s) 363–378

MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/therapy ; Pluripotent Stem Cells
Language	English
Publishing date	2023-06-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/bs.pmbts.2023.03.001
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Article ; Online: pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug.

Kannaujiya, Vinod K / Qiao, Yijie / Sheikh, Rakib H / Xue, Jueyi / Dargaville, Tim R / Liang, Kang / Wich, Peter R

Biomacromolecules

2024 Volume 25, Issue 3, Page(s) 1775–1789

Abstract: The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self- ... ...

Abstract	The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self-amplify and respond to reactive oxygen species (ROS). For this, we incorporated the intracellular ROS generator cinnamaldehyde into a ROS-cleavable thioacetal (TA) linker to obtain the dimeric prodrug of CPT (DCPT(TA)). For its efficient NP delivery, a pH-responsive block copolymer of acetalated dextran and poly(2-ethyl-2-oxazoline) (AcDex-
MeSH term(s)	Humans ; Prodrugs/pharmacology ; Micelles ; Reactive Oxygen Species ; HeLa Cells ; Camptothecin/pharmacology ; Nanoparticles ; Polymers ; Hydrogen-Ion Concentration ; Drug Delivery Systems
Chemical Substances	Prodrugs ; Micelles ; Reactive Oxygen Species ; Camptothecin (XT3Z54Z28A) ; Polymers
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Journal Article
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.3c01240
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Article ; Online: Cell delivery systems: Toward the next generation of cell therapies for type 1 diabetes.

Dang, Hoang Phuc / Chen, Hui / Dargaville, Tim R / Tuch, Bernard E

Journal of cellular and molecular medicine

2022 Volume 26, Issue 18, Page(s) 4756–4767

Abstract: Immunoprotection and oxygen supply are vital in implementing a cell therapy for type 1 diabetes (T1D). Without these features, the transplanted islet cell clusters will be rejected by the host immune system, and necrosis will occur due to hypoxia. The ... ...

Abstract	Immunoprotection and oxygen supply are vital in implementing a cell therapy for type 1 diabetes (T1D). Without these features, the transplanted islet cell clusters will be rejected by the host immune system, and necrosis will occur due to hypoxia. The use of anti-rejection drugs can help protect the transplanted cells from the immune system; yet, they also may have severe side effects. Cell delivery systems (CDS) have been developed for islet transplantation to avoid using immunosuppressants. CDS provide physical barriers to reduce the immune response and chemical coatings to reduce host fibrotic reaction. In some CDS, there is architecture to support vascularization, which enhances oxygen exchange. In this review, we discuss the current clinical and preclinical studies using CDS without immunosuppression as a cell therapy for T1D. We find that though CDS have been demonstrated for their ability to support immunoisolation of the grafted cells, their functionality has not been fully optimized. Current advanced methods in clinical trials demonstrate the systems are partly functional, physically complicated to implement or inefficient. However, modifications are being made to overcome these issues.
MeSH term(s)	Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 1/therapy ; Humans ; Immunosuppression Therapy ; Islets of Langerhans/metabolism ; Islets of Langerhans Transplantation/methods ; Oxygen/metabolism
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2022-08-16
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.17499
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Article: Stability of Inhaled Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticle Dry Powder Inhaler Formulation in High Stressed Conditions.

Sabuj, Mohammad Zaidur Rahman / Rashid, Md Abdur / Dargaville, Tim R / Islam, Nazrul

Pharmaceuticals (Basel, Switzerland)

2022 Volume 15, Issue 10

Abstract: In this study, the stability of ciprofloxacin (CIP)-loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) was investigated at normal and high stressed conditions. The blank NPs were used to understand the intrinsic physicochemical properties of ... ...

Abstract	In this study, the stability of ciprofloxacin (CIP)-loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) was investigated at normal and high stressed conditions. The blank NPs were used to understand the intrinsic physicochemical properties of the polymer NPs under these storage conditions. The formulated NPs were prepared by a coassembly reaction and dried by lyophilization. The powder NPs were stored at controlled room temperature (25 °C) with normal relative humidity (RH) (43%) and high temperature (40 °C) and RH (75%). The stored samples were analyzed by determining the particle sizes, morphology, solid-state properties, thermal behavior, drug-polymer interactions, and aerosol performances over six months. The chemical stability of the formulations was determined by X-ray diffraction, attenuated total refection-Fourier transform infrared (ATR-FTIR), and high-performance liquid chromatography (HPLC) over six months under both conditions. The particle size of the blank PEtOx NPs significantly (p < 0.05) increased from 195.4 nm to 202.7 nm after 3 months at 40 °C/75% RH due to the moisture absorption from high RH; however, no significant increase was observed afterward. On the other hand, the sizes of CIP-loaded PEtOx NPs significantly (p < 0.05) reduced from 200.2 nm to 126.3 nm after 6 months at 40 °C/75% RH. In addition, the scanning electron microscopy (SEM) images revealed that the surfaces of CIP-loaded PEtOx NPs become smoother after 3 months of storage due to the decay of surface drugs compared to the freshly prepared NPs. However, transmission electron microscopy (TEM) images could not provide much information on drug decay from the nanoparticle’s surfaces. The fine particle fraction (FPF) of CIP-loaded PEtOx NPs dropped significantly (p < 0.05) after three months at 25 °C/43% RH and 40 °C/75% RH conditions. The reduced FPF of CIP-loaded PEtOx NPs occurred due to the drug decay from the polymeric surface and blank PEtOx NPs due to the aggregations of the NPs at high temperatures and RH. Although the aerosolization properties of the prepared CIP-loaded PEtOx NPs were reduced, all formulations were chemically stable in the experimental conditions.
Language	English
Publishing date	2022-10-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph15101223
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Article: Opinion to address the personal protective equipment shortage in the global community during the COVID-19 outbreak.

Dargaville, Tim / Spann, Kirsten / Celina, Mathew

Polymer degradation and stability

2020 Volume 176, Page(s) 109162

Abstract: The current COVID-19 pandemic is stretching both the global supply for face masks and personal protective equipment (PPE). Production capacity is severely limited in many countries. This is a call for the R&D community, particularly to those in the ... ...

Abstract	The current COVID-19 pandemic is stretching both the global supply for face masks and personal protective equipment (PPE). Production capacity is severely limited in many countries. This is a call for the R&D community, particularly to those in the polymer degradation and stability field. We have not only an opportunity but an obligation to engage and collaborate with virology and bio-medical experts. We require comparative R&D for extended, reuse and recyclability options. There is urgent need for large scale institutional approaches and methods that can be quickly applied locally by non-experts with limited resources.
Keywords	covid19
Language	English
Publishing date	2020-04-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1502217-1
ISSN	0141-3910
ISSN	0141-3910
DOI	10.1016/j.polymdegradstab.2020.109162
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Article ; Online: Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide.

Sabuj, Mohammad Zaidur Rahman / Huygens, Flavia / Spann, Kirsten M / Tarique, Abdullah A / Dargaville, Tim R / Will, Geoffrey / Wahab, Md Abdul / Islam, Nazrul

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: The bactericidal effects of inhalable ciprofloxacin (CIP) loaded-poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) with traces of zinc oxide (ZnO) were investigated against clinical strains of the respiratory ... ...

Abstract	The bactericidal effects of inhalable ciprofloxacin (CIP) loaded-poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) with traces of zinc oxide (ZnO) were investigated against clinical strains of the respiratory pathogens
MeSH term(s)	Humans ; Ciprofloxacin/pharmacology ; Zinc Oxide/chemistry ; Anti-Bacterial Agents/pharmacology ; Nanoparticles/chemistry ; Spectroscopy, Fourier Transform Infrared ; Pulmonary Disease, Chronic Obstructive ; Metal Nanoparticles/chemistry ; Microbial Sensitivity Tests
Chemical Substances	Ciprofloxacin (5E8K9I0O4U) ; Zinc Oxide (SOI2LOH54Z) ; poly(2-ethyl-2-oxazoline) ; Anti-Bacterial Agents
Language	English
Publishing date	2023-02-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054532
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Article ; Online: Inhaled ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) nanoparticles from dry powder inhaler formulation for the potential treatment of lower respiratory tract infections.

Sabuj, Mohammad Zaidur Rahman / Dargaville, Tim R / Nissen, Lisa / Islam, Nazrul

PloS one

2021 Volume 16, Issue 12, Page(s) e0261720

Abstract: Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses ... ...

Abstract	Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses with frequent administration and cause dose-related adverse effects. To overcome this problem, we investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs. NPs were prepared using a straightforward co-assembly reaction carried out by the intermolecular hydrogen bonding among PEtOx, tannic acid (TA), and CIP. The prepared NPs were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The CIP was determined by validated HPLC and UV spectrophotometry methods. The CIP loading into the PEtOx was between 21-67% and increased loading was observed with the increasing concentration of CIP. The NP sizes of PEtOx with or without drug loading were between 196-350 nm and increased with increasing drug loading. The in vitro CIP release showed the maximum cumulative release of about 78% in 168 h with a burst release of 50% in the first 12 h. The kinetics of CIP release from NPs followed non-Fickian or anomalous transport thus suggesting the drug release was regulated by both diffusion and polymer degradation. The in vitro aerosolization study carried out using a Twin Stage Impinger (TSI) at 60 L/min air flow showed the fine particle fraction (FPF) between 34.4% and 40.8%. The FPF was increased with increased drug loading. The outcome of this study revealed the potential of the polymer PEtOx as a carrier for developing CIP-loaded PEtOx NPs as DPI formulation for pulmonary delivery against LRTIs.
MeSH term(s)	Administration, Inhalation ; Ciprofloxacin/chemistry ; Ciprofloxacin/pharmacokinetics ; Drug Carriers/chemistry ; Drug Carriers/pharmacokinetics ; Dry Powder Inhalers ; Humans ; Nanoparticles/chemistry ; Polyamines/chemistry ; Polyamines/pharmacokinetics
Chemical Substances	Drug Carriers ; Polyamines ; poly(2-ethyl-2-oxazoline) ; Ciprofloxacin (5E8K9I0O4U)
Language	English
Publishing date	2021-12-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0261720
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Article ; Online: Enhanced clearance of C. muridarum infection using azithromycin-loaded liposomes.

Arasu, Yanushia / Bryan, Emily / Russell, Freya A / Huettner, Nick / Carey, Alison J / Boyd, Ben J / Beagley, Kenneth W / Dargaville, Tim R

International journal of pharmaceutics

2023 Volume 650, Page(s) 123709

Abstract: Chlamydia trachomatis is an intracellular bacterium which infects around 129 million people annually. Despite similar infection rates between sexes, most research investigating the effects of chlamydial infection on fertility has focused on females. ... ...

Abstract	Chlamydia trachomatis is an intracellular bacterium which infects around 129 million people annually. Despite similar infection rates between sexes, most research investigating the effects of chlamydial infection on fertility has focused on females. There is now emerging evidence of a potential link between Chlamydia and impaired male fertility. The only treatments for chlamydial infection are antibiotics, with azithromycin (AZI) being one of the commonly used drugs. However, recent studies have suggested that optimizing the treatment regime is necessary, as higher concentrations of AZI may be required to effectively clear the infection in certain cell types, particularly testicular macrophages. To address this challenge, we have prepared liposomes consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) loaded with AZI for clearing Chlamydia. These liposomes exhibited stability over time and were readily taken up by both macrophages and epithelial cells. Moreover, they demonstrated significant enhancement of chlamydial clearance in both cell types. In a mouse model, the drug-loaded liposomes cleared Chlamydia within the penile urethra more efficiently than the same dose of unencapsulated drug. Furthermore, the liposome-drug treatment showed significant protective effects on sperm motility and morphology, suggesting potential benefits in reducing sperm damage caused by the infection.
MeSH term(s)	Mice ; Female ; Animals ; Male ; Humans ; Azithromycin/pharmacology ; Liposomes/pharmacology ; Semen ; Sperm Motility ; Chlamydia Infections/drug therapy ; Chlamydia trachomatis
Chemical Substances	Azithromycin (83905-01-5) ; Liposomes
Language	English
Publishing date	2023-12-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2023.123709
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Article ; Online: Direct ink writing of multifunctional nanocellulose and allyl-modified gelatin biomaterial inks for the fabrication of mechanically and functionally graded constructs.

Cianciosi, Alessandro / Simon, Jonas / Bartolf-Kopp, Michael / Grausgruber, Heinrich / Dargaville, Tim R / Forget, Aurélien / Groll, Jürgen / Jungst, Tomasz / Beaumont, Marco

Carbohydrate polymers

2023 Volume 319, Page(s) 121145

Abstract: Recreating the intricate mechanical and functional gradients found in natural tissues through additive manufacturing poses significant challenges, including the need for precise control over time and space and the availability of versatile biomaterial ... ...

Abstract	Recreating the intricate mechanical and functional gradients found in natural tissues through additive manufacturing poses significant challenges, including the need for precise control over time and space and the availability of versatile biomaterial inks. In this proof-of-concept study, we developed a new biomaterial ink for direct ink writing, allowing the creation of 3D structures with tailorable functional and mechanical gradients. Our ink formulation combined multifunctional cellulose nanofibrils (CNFs), allyl-functionalized gelatin (0.8-2.0 wt%), and polyethylene glycol dithiol (3.0-7.5 wt%). The CNF served as a rheology modifier, whereas a concentration of 1.8 w/v % in the inks was chosen for optimal printability and shape fidelity. In addition, CNFs were functionalized with azido groups, enabling the spatial distribution of functional moieties within a 3D structure. These functional groups were further modified using a spontaneous click chemistry reaction. Through additive manufacturing and a readily available static mixer, we successfully demonstrated the fabrication of mechanical gradients - ranging from 3 to 6 kPa in indentation strength - and functional gradients. Additionally, we introduced dual gradients by combining gradient printing with an anisotropic photocrosslinking step. The developed biomaterial ink opens up possibilities for printing intricate multigradient structures, resembling the complex hierarchical organization seen in living tissues.
Language	English
Publishing date	2023-06-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2023.121145
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Article ; Online: Thermoresponsive Polymer-Antibiotic Conjugates Based on Gradient Copolymers of 2-Oxazoline and 2-Oxazine.

Park, Jong-Ryul / Verderosa, Anthony D / Totsika, Makrina / Hoogenboom, Richard / Dargaville, Tim R

Biomacromolecules

2021 Volume 22, Issue 12, Page(s) 5185–5194

Abstract: A polymer-antibiotic conjugate with thermoresponsive properties near body temperature is presented. The backbone polymer is a copolymer of 2- ...

Abstract	A polymer-antibiotic conjugate with thermoresponsive properties near body temperature is presented. The backbone polymer is a copolymer of 2-
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Micelles ; Oxazines ; Polymers ; Temperature
Chemical Substances	Anti-Bacterial Agents ; Micelles ; Oxazines ; Polymers
Language	English
Publishing date	2021-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.1c01133
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