Drug Loading in Poly(butyl cyanoacrylate)-Based Polymeric Microbubbles.

Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. To better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties, and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e., for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e., four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.

Health service utilisation and unmet healthcare needs of Australian children from immigrant families: A population-based cohort study.

Compared with most other Organization for Economic Co-operation and Development (OECD) countries, information about the patterns of health service use for children from immigrant families in Australia is currently limited, and internationally, data on unmet healthcare needs are scarce. This study aims to examine the distribution of health service utilisation and unmet healthcare needs for immigrant children aged 10-11 years in Australia. We drew on data from the Longitudinal Study of Australian Children Birth (B; n = 5,107) and Kindergarten (K; n = 4,983) cohorts. The exposure was family immigration background collected at 0-1 (B-cohort) and 4-5 (K-cohort) years. Outcomes were parent-reported child health service use and unmet healthcare needs (defined as the difference between services needed and services received) at 10-11 years. Logistic regression analyses were used to examine associations between family immigration background and health service use/unmet healthcare needs, adjusting for potential confounders. Results showed that one-third of Australian children (B-cohort: 29.0%; K-cohort: 33.4%) came from immigrant families. There were similar patterns of health service use and unmet healthcare needs between children from English-speaking immigrant and Australian-born families. However, children from non-English-speaking immigrant families used fewer health services, including paediatric, dental, mental health and emergency ward services. There was a disparity between the services used when considering children's health needs, particularly for paediatric specialist services (B-cohort: OR = 2.43, 95% CI 1.11-5.31; K-cohort: OR = 2.72, 95% CI 1.32-5.58). Findings indicate that Australian children from non-English-speaking immigrant families experience more unmet healthcare needs and face more barriers in accessing health services. Further effort is needed to ensure that the healthcare system meets the needs of all families.

Poloxamer modified florfenicol instant microparticles for improved oral bioavailability.

Surfactants can improve the hydrophobicity of poorly water-soluble drugs and increase the stability of microparticles by reducing surface tension. This study describes that surfactant-engineered florfenicol instant microparticles (FIMs) increase bioavailability through a micellar solubilization mechanism. The FIMs were prepared by a modified emulsification method, and the optimal prescription was obtained by a combination of single factor investigation and response surface methodology. The microparticles prepared in this study reduce the polymer materials while increasing the drug content. FIM has a smaller particle size and modification of poloxamer, resulting in better solubility and higher bioavailability. The in vitro solubility of FIM is 1.43 times higher than that of the bulk drug, and the dissolution equilibrium can be achieved in 10 minutes. Compared with florfenicol, FIM showed a decrease in Tmax in the plasma concentration curve, with a peak concentration of 1.43 times and an area of 1.41 times. Considering the advantages of in vitro/in vivo performance and ease of preparation, FIMs may have great application prospects in pharmacy research.

PBCA-based polymeric microbubbles for molecular imaging and drug delivery.

Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated drug delivery. Molecular imaging of angiogenic tumor blood vessels and inflamed atherosclerotic endothelium is performed by modifying the surface of PBCA MB with peptides and antibodies recognizing E-selectin and VCAM-1. Stable and inertial cavitation of PBCA MB enables sonoporation and permeabilization of blood vessels in tumors and in the brain, which can be employed for direct and indirect drug delivery. Direct drug delivery is based on US-induced release of (model) drug molecules from the MB shell. Indirect drug delivery refers to US- and MB-mediated enhancement of extravasation and penetration of co-administered drugs and drug delivery systems. These findings are in line with recently reported pioneering proof-of-principle studies showing the usefulness of (phospholipid) MB for molecular US imaging and sonoporation-enhanced drug delivery in patients. They aim to exemplify the potential and the broad applicability of combining MB with US to improve disease diagnosis and therapy.

Novel thermosensitive in situ gel based on poloxamer for uterus delivery.

Side effects and drug residues are major concerns affecting hormone therapy of bovine reproductive diseases. Fertility-promoting intrauterine infusion liquid (FPL), an effective alternative to hormone therapy, is associated with short retention time and low therapeutic efficacy. To address these problems, we developed a thermosensitive in situ gel based on poloxamer 407 for local uterine administration. To achieve the desired gelling temperature and enhance local retention property, we added poloxamer 188 and HPMC to the formulation containing poloxamer 407 and FPL. After screening was performed, the optimized formulation showed good temperature sensitivity in vitro and in vivo. Gelation temperature was approximately 27°C. In vitro release tests showed that icariin (the major active compound in FPL) was slow released from in situ forming gel. After the gel was locally administered, uterine and ovarian indexes were significantly increased in the gel group compared with the control group (P<0.05). The serum estradiol level of the gel group was significantly higher than that of the control group (P<0.01). Histological evaluation did not show mucosa irritation in the gel group. Therefore, the proposed in situ forming gel system based on poloxamer 407 is a promising local drug delivery system to treat bovine uterine diseases.