Melt-electrospinning as a method to improve the dissolution and physical stability of a poorly water-soluble drug

The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus (R) (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(H-1), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).Peer reviewe

Comparison of Traditional and Ultrasound-Enhanced Electrospinning in Fabricating Nanofibrous Drug Delivery Systems

We investigated nozzleless ultrasound-enhanced electrospinning (USES) as means to generate nanofibrous drug delivery systems (DDSs) for pharmaceutical and biomedical applications. Traditional electrospinning (TES) equipped with a conventional spinneret was used as a reference method. High-molecular polyethylene oxide (PEO) and chitosan were used as carrier polymers and theophylline anhydrate as a water-soluble model drug. The nanofibers were electrospun with the diluted mixture (7:3) of aqueous acetic acid (90% v/v) and formic acid solution (90% v/v) (with a total solid content of 3% w/v). The fiber diameter and morphology of the nanofibrous DDSs were modulated by varying ultrasonic parameters in the USES process (i.e., frequency, pulse repetition frequency and cycles per pulse). We found that the USES technology produced nanofibers with higher fiber diameter (402 ± 127 nm) than TES (77 ± 21 nm). An increase of a burst count in USES increased the fiber diameter (555 ± 265 nm) and the variation in fiber size. The slight-to-moderate changes in a solid state (crystallinity) were detected when compared the nanofibers generated by TES and USES. In conclusion, USES provides a promising alternative for aqueous-based fabrication of nanofibrous DDSs for pharmaceutical and biomedical applications

Comparison of Traditional and Ultrasound-Enhanced Electrospinning in Fabricating Nanofibrous Drug Delivery Systems

We investigated nozzleless ultrasound-enhanced electrospinning (USES) as means to generate nanofibrous drug delivery systems (DDSs) for pharmaceutical and biomedical applications. Traditional electrospinning (TES) equipped with a conventional spinneret was used as a reference method. High-molecular polyethylene oxide (PEO) and chitosan were used as carrier polymers and theophylline anhydrate as a water-soluble model drug. The nanofibers were electrospun with the diluted mixture (7:3) of aqueous acetic acid (90% v/v) and formic acid solution (90% v/v) (with a total solid content of 3% w/v). The fiber diameter and morphology of the nanofibrous DDSs were modulated by varying ultrasonic parameters in the USES process (i.e., frequency, pulse repetition frequency and cycles per pulse). We found that the USES technology produced nanofibers with higher fiber diameter (402 ± 127 nm) than TES (77 ± 21 nm). An increase of a burst count in USES increased the fiber diameter (555 ± 265 nm) and the variation in fiber size. The slight-to-moderate changes in a solid state (crystallinity) were detected when compared the nanofibers generated by TES and USES. In conclusion, USES provides a promising alternative for aqueous-based fabrication of nanofibrous DDSs for pharmaceutical and biomedical applications

Inequity of antenatal influenza and pertussis vaccine coverage in Australia: the Links2HealthierBubs record linkage cohort study, 2012–2017

Background: Pregnancy and early infancy are increased risk periods for severe adverse effects of respiratory infections. Aboriginal and/or Torres Strait Islander (respectfully referred to as First Nations) women and children in Australia bear a disproportionately higher burden of respiratory diseases compared to non-Indigenous women and infants. Influenza vaccines and whooping cough (pertussis) vaccines are recommended and free in every Australian pregnancy to combat these infections. We aimed to assess the equity of influenza and/or pertussis vaccination in pregnancy for three priority groups in Australia: First Nations women; women from culturally and linguistically diverse (CALD) backgrounds; and women living in remote areas or socio-economic disadvantage. Methods: We conducted individual record linkage of Perinatal Data Collections with immunisation registers/databases between 2012 and 2017. Analysis included generalised linear mixed model, log-binomial regression with a random intercept for the unique maternal identifier to account for clustering, presented as prevalence ratios (PR) and 95% compatibility intervals (95%CI). Results: There were 445,590 individual women in the final cohort. Compared with other Australian women (n = 322,848), First Nations women (n = 29,181) were less likely to have received both recommended antenatal vaccines (PR 0.69, 95% CI 0.67–0.71) whereas women from CALD backgrounds (n = 93,561) were more likely to have (PR 1.16, 95% CI 1.10–1.13). Women living in remote areas were less likely to have received both vaccines (PR 0.75, 95% CI 0.72–0.78), and women living in the highest areas of advantage were more likely to have received both vaccines (PR 1.44, 95% CI 1.40–1.48). Conclusions: Compared to other groups, First Nations Australian families, those living in remote areas and/or families from lower socio-economic backgrounds did not receive recommended vaccinations during pregnancy that are the benchmark of equitable healthcare. Addressing these barriers must remain a core priority for Australian health care systems and vaccine providers. An extension of this cohort is necessary to reassess these study findings

\u27Links2HealthierBubs\u27 cohort study: Protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women

Introduction: Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. Methods and analysis: ‘Links2HealthierBubs’ is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. Ethics and dissemination: Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women’s Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public

Multifaceted link between cancer and inflammation

10.1042/BSR20100136Bioscience Reports3211-15BRPT