Jesse Xu | The University of Sydney (original) (raw)
Papers by Jesse Xu
Drug Development and Industrial Pharmacy
Respiratory Drug Delivery 2018, 2018
Drug development and industrial pharmacy, Jan 25, 2018
Airway stents are commonly used in the management of patients suffering from central airway obstr... more Airway stents are commonly used in the management of patients suffering from central airway obstruction (CAO). CAO may occur directly from airway strictures, obstructing airway cancers, airway fistulas or tracheobronchomalacia, resulting from the weakening and dynamic collapse of the airway wall. Current airway stents are constructed from biocompatible medical-grade silicone or from a nickel-titanium (nitinol) alloy with fixed geometry. The stents are inserted via the mouth during a bronchoscopic procedure. Existing stents have many shortcomings including the development of obstructing granulation tissue in the weeks and months following placement, mucous build up within the stent, and cough. Furthermore, airway stents are expensive and, if improperly sized for a given airway, may be easily dislodged (stent migration). Currently, in Australia, it is estimated that approximately 12,000 patients will develop CAO annually, many of whom will require airway stenting intervention. Of all ...
Expert Opinion on Drug Delivery, 2020
ABSTRACT Background Airway stents are used to treat obstructive central airway pathologies includ... more ABSTRACT Background Airway stents are used to treat obstructive central airway pathologies including palliation of lung cancer, but face challenges with granulation tissue growth. Paclitaxel is a chemotherapy drug that also suppresses growth of granulation tissue. Yet, side effects arise from administration with toxic solubilizers. By incorporating paclitaxel in silicone stents, delivery of paclitaxel can be localized, and side effects minimized. Methods Paclitaxel was incorporated into Liquid Silicone Rubber (LSR) containing polydimethylsiloxane, either as a powder or solution, prior to curing. Drug release study was compared in vitro at 37°C over 10 days. Drug release was quantified using HPLC, and bronchial cell lines were grown on LSR to investigate drug cytotoxicity, and expression of inflammatory markers, specifically interleukin-6 and interleukin-8. Results Release rate of paclitaxel incorporated into silicone rubber was consistent with the Korsmeyer and Weibull models (R2 > 0.96). Paclitaxel exposure reduced IL-8 levels in cancer cell lines, whilst no cytotoxic effect was observed in all cell lines at treatment concentration levels (≤ 0.1% (w/v) paclitaxel in silicone). Conclusions Incorporating paclitaxel into a silicone matrix for future use in a tracheobronchial stent was investigated. Drug release from silicone was observed and is a promising avenue for future treatments of central airway pathologies.
Interactive CardioVascular and Thoracic Surgery
Airway stents are used to manage central airway obstructions by restoring airway patency. Current... more Airway stents are used to manage central airway obstructions by restoring airway patency. Current manufactured stents are limited in shape and size, which pose issues in stent fenestrations needed to be manually created to allow collateral ventilation to airway branches. The precise location to place these fenestrations can be difficult to predict based on 2-dimensional computed tomography images. Inspiratory computed tomography scans were obtained from 3 patients and analysed using 3D-Slicer™, Blender™ and AutoDesk® Meshmixer™ programmes to obtain working 3D-airway models, which were 3D printed. Stent customizations were made based on 3D-model dimensions, and fenestrations into the stent were cut. The modified stents were then inserted as per usual technique. Two patients reported improved airway performance; however, stents were later removed due to symptoms related to in-stent sputum retention. In a third patient, the stent was removed a few weeks later due to the persistence of ...
Airway stents are commonly used in the management of patients suffering from central airway obstr... more Airway stents are commonly used in the management of patients suffering from central airway obstruc- tion (CAO). CAO may occur directly from airway strictures, obstructing airway cancers, airway fistulas or tracheobronchomalacia, resulting from the weakening and dynamic collapse of the airway wall. Current airway stents are constructed from biocompatible medical-grade silicone or from a nickel–titanium (nitinol) alloy with fixed geometry. The stents are inserted via the mouth during a bronchoscopic procedure. Existing stents have many shortcomings including the development of obstructing granulation tissue in the weeks and months following placement, mucous build up within the stent, and cough. Furthermore, airway stents are expensive and, if improperly sized for a given airway, may be easily dislodged (stent migration). Currently, in Australia, it is estimated that approximately 12,000 patients will develop CAO annually, many of whom will require airway stenting intervention. Of all stenting procedures, the rate of failure is currently reported to be at 22%. With a growing incidence of lung cancer prevalence globally, the need for updating airway stent technology is now greater than ever and personalizing stents using 3D-printing technology may offer the best chance of addressing many of the current limitations in stent design. This review article will assess what represents the gold standard in stent manufacture with regards to treatment of tracheobronchial CAO, the challenges of current airway stents, and outlines the necessity and challenges of incorporating 3D-printing technology into personalizing airway stents today.
Pulmonary Arterial Hypertension (PAH) is a rare condition characterised by increased vascular res... more Pulmonary Arterial Hypertension (PAH) is a rare condition characterised by increased vascular resistance in the pulmonary arteries, and are often associated with right heart failure at the final stages of pathogenesis (Bajwa et al., 2015). Normal blood flow from the pulmonary arteries leads from the right ventricles in the heart to the visceral lung. In PAH, this causes increased vascular resistance in the right ventricles from backlog, and eventually right heart failure (Marra et al., 2015). Treatment options have improved the outlook of PAH patients since the introduction of calcium channel blocker therapy in 1989 (Medarov & Judson, 2015), and the improved stability and half-lives of prostanoids. Despite these progresses, mortality rates remains high with median life expectancy rising from 2.8 years to 6.7 years in the past 20 years.
The progress of improving treatments for primary PAH (PPAH) is limited due to a plethora of potential sources of vascular remodelling pathways that are involved with the disease, causing heterogeneity. Current therapies only target a small proportion of the signalling pathways associated with PPAH pathogenesis, with particular focus on manipulating the role of endothelin, prostacyclin and nitric oxide signalling pathways (Van Hung et al., 2014) . More recently, it has been considered that combination therapy with the targeting of multiple signalling pathways with drugs may have a more significant effect in improving treatment of PPAH (Galie, 2015). However, this also introduces issues of polypharmacy and considerations of adverse drug reactions and patient compliance. Further emerging treatments of PAH are also focusing on alleviation of symptoms in PPAH, since PPAH is a highly morbid disease, as observed in vastly reduced patient’s performance in the 6-minute walk test (6MWT).
Caffeine is a widely consumed methylxanthine drug found naturally in tea, coffee and the cocoa pl... more Caffeine is a widely consumed methylxanthine drug found naturally in tea, coffee and the cocoa plant, with an average adult consumption of 2.4mg/kg/day (Echeverri et al, 2010). The stimulatory properties of methylxanthine drugs are caused primarily by the non-selective antagonism of Gαi and Gαo protein coupled adenosine A1 and A2A receptors (Hsu et al, 2009). Since, adenosine receptors are involved in the inhibition of neurotransmitter release, the antagonism of these receptors are stimulatory. The antagonism of A1 receptors is known to stimulate heart rate (HR) via ionotropic and chronotropic effects. As a consequence, caffeine has been found to increase HR (Echeverri et al, 2010). The inhibitory effects of A2A receptors is more widely expressed in the cerebral regions that are involved in dopaminergic innervation, including the dorsal striatum, nucleus accumbens (NAc), and olfactory tubercle (Hsu et al, 2009). As a consequence, caffeine is widely regarded to have a large role in the central nervous system, to stimulate neurotransmitter release.
Drug Development and Industrial Pharmacy
Respiratory Drug Delivery 2018, 2018
Drug development and industrial pharmacy, Jan 25, 2018
Airway stents are commonly used in the management of patients suffering from central airway obstr... more Airway stents are commonly used in the management of patients suffering from central airway obstruction (CAO). CAO may occur directly from airway strictures, obstructing airway cancers, airway fistulas or tracheobronchomalacia, resulting from the weakening and dynamic collapse of the airway wall. Current airway stents are constructed from biocompatible medical-grade silicone or from a nickel-titanium (nitinol) alloy with fixed geometry. The stents are inserted via the mouth during a bronchoscopic procedure. Existing stents have many shortcomings including the development of obstructing granulation tissue in the weeks and months following placement, mucous build up within the stent, and cough. Furthermore, airway stents are expensive and, if improperly sized for a given airway, may be easily dislodged (stent migration). Currently, in Australia, it is estimated that approximately 12,000 patients will develop CAO annually, many of whom will require airway stenting intervention. Of all ...
Expert Opinion on Drug Delivery, 2020
ABSTRACT Background Airway stents are used to treat obstructive central airway pathologies includ... more ABSTRACT Background Airway stents are used to treat obstructive central airway pathologies including palliation of lung cancer, but face challenges with granulation tissue growth. Paclitaxel is a chemotherapy drug that also suppresses growth of granulation tissue. Yet, side effects arise from administration with toxic solubilizers. By incorporating paclitaxel in silicone stents, delivery of paclitaxel can be localized, and side effects minimized. Methods Paclitaxel was incorporated into Liquid Silicone Rubber (LSR) containing polydimethylsiloxane, either as a powder or solution, prior to curing. Drug release study was compared in vitro at 37°C over 10 days. Drug release was quantified using HPLC, and bronchial cell lines were grown on LSR to investigate drug cytotoxicity, and expression of inflammatory markers, specifically interleukin-6 and interleukin-8. Results Release rate of paclitaxel incorporated into silicone rubber was consistent with the Korsmeyer and Weibull models (R2 > 0.96). Paclitaxel exposure reduced IL-8 levels in cancer cell lines, whilst no cytotoxic effect was observed in all cell lines at treatment concentration levels (≤ 0.1% (w/v) paclitaxel in silicone). Conclusions Incorporating paclitaxel into a silicone matrix for future use in a tracheobronchial stent was investigated. Drug release from silicone was observed and is a promising avenue for future treatments of central airway pathologies.
Interactive CardioVascular and Thoracic Surgery
Airway stents are used to manage central airway obstructions by restoring airway patency. Current... more Airway stents are used to manage central airway obstructions by restoring airway patency. Current manufactured stents are limited in shape and size, which pose issues in stent fenestrations needed to be manually created to allow collateral ventilation to airway branches. The precise location to place these fenestrations can be difficult to predict based on 2-dimensional computed tomography images. Inspiratory computed tomography scans were obtained from 3 patients and analysed using 3D-Slicer™, Blender™ and AutoDesk® Meshmixer™ programmes to obtain working 3D-airway models, which were 3D printed. Stent customizations were made based on 3D-model dimensions, and fenestrations into the stent were cut. The modified stents were then inserted as per usual technique. Two patients reported improved airway performance; however, stents were later removed due to symptoms related to in-stent sputum retention. In a third patient, the stent was removed a few weeks later due to the persistence of ...
Airway stents are commonly used in the management of patients suffering from central airway obstr... more Airway stents are commonly used in the management of patients suffering from central airway obstruc- tion (CAO). CAO may occur directly from airway strictures, obstructing airway cancers, airway fistulas or tracheobronchomalacia, resulting from the weakening and dynamic collapse of the airway wall. Current airway stents are constructed from biocompatible medical-grade silicone or from a nickel–titanium (nitinol) alloy with fixed geometry. The stents are inserted via the mouth during a bronchoscopic procedure. Existing stents have many shortcomings including the development of obstructing granulation tissue in the weeks and months following placement, mucous build up within the stent, and cough. Furthermore, airway stents are expensive and, if improperly sized for a given airway, may be easily dislodged (stent migration). Currently, in Australia, it is estimated that approximately 12,000 patients will develop CAO annually, many of whom will require airway stenting intervention. Of all stenting procedures, the rate of failure is currently reported to be at 22%. With a growing incidence of lung cancer prevalence globally, the need for updating airway stent technology is now greater than ever and personalizing stents using 3D-printing technology may offer the best chance of addressing many of the current limitations in stent design. This review article will assess what represents the gold standard in stent manufacture with regards to treatment of tracheobronchial CAO, the challenges of current airway stents, and outlines the necessity and challenges of incorporating 3D-printing technology into personalizing airway stents today.
Pulmonary Arterial Hypertension (PAH) is a rare condition characterised by increased vascular res... more Pulmonary Arterial Hypertension (PAH) is a rare condition characterised by increased vascular resistance in the pulmonary arteries, and are often associated with right heart failure at the final stages of pathogenesis (Bajwa et al., 2015). Normal blood flow from the pulmonary arteries leads from the right ventricles in the heart to the visceral lung. In PAH, this causes increased vascular resistance in the right ventricles from backlog, and eventually right heart failure (Marra et al., 2015). Treatment options have improved the outlook of PAH patients since the introduction of calcium channel blocker therapy in 1989 (Medarov & Judson, 2015), and the improved stability and half-lives of prostanoids. Despite these progresses, mortality rates remains high with median life expectancy rising from 2.8 years to 6.7 years in the past 20 years.
The progress of improving treatments for primary PAH (PPAH) is limited due to a plethora of potential sources of vascular remodelling pathways that are involved with the disease, causing heterogeneity. Current therapies only target a small proportion of the signalling pathways associated with PPAH pathogenesis, with particular focus on manipulating the role of endothelin, prostacyclin and nitric oxide signalling pathways (Van Hung et al., 2014) . More recently, it has been considered that combination therapy with the targeting of multiple signalling pathways with drugs may have a more significant effect in improving treatment of PPAH (Galie, 2015). However, this also introduces issues of polypharmacy and considerations of adverse drug reactions and patient compliance. Further emerging treatments of PAH are also focusing on alleviation of symptoms in PPAH, since PPAH is a highly morbid disease, as observed in vastly reduced patient’s performance in the 6-minute walk test (6MWT).
Caffeine is a widely consumed methylxanthine drug found naturally in tea, coffee and the cocoa pl... more Caffeine is a widely consumed methylxanthine drug found naturally in tea, coffee and the cocoa plant, with an average adult consumption of 2.4mg/kg/day (Echeverri et al, 2010). The stimulatory properties of methylxanthine drugs are caused primarily by the non-selective antagonism of Gαi and Gαo protein coupled adenosine A1 and A2A receptors (Hsu et al, 2009). Since, adenosine receptors are involved in the inhibition of neurotransmitter release, the antagonism of these receptors are stimulatory. The antagonism of A1 receptors is known to stimulate heart rate (HR) via ionotropic and chronotropic effects. As a consequence, caffeine has been found to increase HR (Echeverri et al, 2010). The inhibitory effects of A2A receptors is more widely expressed in the cerebral regions that are involved in dopaminergic innervation, including the dorsal striatum, nucleus accumbens (NAc), and olfactory tubercle (Hsu et al, 2009). As a consequence, caffeine is widely regarded to have a large role in the central nervous system, to stimulate neurotransmitter release.