Functional engineering of microneedles for transdermal drug delivery

Microneedles (MNs) have emerged as a promising platform for effective transdermal drug delivery because of its non-invasiveness, ease of application, and ability to ensure controlled and targeted drug delivery. However, there is a lack of solutions to resolve several shortcomings related to applications of MN (potential bacterial infection and skin irritation) and its inability as a drug delivery platform to deliver living therapeutics. Two strategies were proposed to address these shortcomings – surface engineering strategy and materials engineering strategy. Surface engineering of MN platform using coating methods was utilized to confer additional functionality to the MN platform. Hydrothermal method was employed to incorporate antibacterial coating on MN, achieving antibacterial functionality. To improve on the fixation issue, nonaqueous dendrimer bioadhesive was coated on the surface of the MN to improve the adhesive strength of the MN platform and allow for hydrophobic drug loading. Next, materials engineering strategy was utilized to achieve effective transdermal cell delivery with MN platform. Cryomicroneedles (cryoMNs) which was conceived from the integration of cryopreservation concept with MN platform was proposed for the loading of cells and spheroids. CryoMNs demonstrate great potential as a platform for cell therapy and tissue regeneration applications.Doctor of Philosoph

Non-invasive imaging of intracellular mRNA dynamics using molecular beacon-based nanosensors

Messenger RNA is a key player in the regulation of cellular activities. Real-time assessment of intracellular mRNA dynamics can offer invaluable insights into the inner workings of cells. Previous imaging techniques suffer from the inefficient delivery of imaging probes into cells and false positive signals due to endonuclease digestion. In this paper, we introduce a novel approach to allow both the control of mRNA expression as well as non-invasive imaging of intracellular mRNA dynamics during gene activation period by incorporating the molecular beacon-based nanosensors into regulated gene expression system – Tet-On system. The molecular beacon-based nanosensors were synthesized by encapsulating mRNA-specific molecular beacons into PLGA nanoparticles. Using Enhanced Green Fluorescence Protein (EGFP) as a case study, the conditions were optimized to ensure efficient nanosensor uptake and optimal EGFP Tet-On system activation. With the activation trend of Tet-On system established, the kinetics of the nanosensors was examined during the gene activation period (0 – 48 hours). The nanosensors exhibited high specificity towards EGFP mRNA and do not interfere with EGFP gene expression. Most importantly, the nanosensors have high specificity and sensitivity towards EGFP mRNA comparable to that of reverse transcription quantitative polymerase chain reaction (RT-PCR).Bachelor of Engineering (Chemical and Biomolecular Engineering

Transdermal delivery of Chinese herbal medicine extract using dissolvable microneedles for hypertrophic scar treatment

Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition. Although systemic treatments exist in clinic to manage hypertrophic scars, they pose significant side effects and tend to lose efficacy over prolonged applications. Traditional Chinese medicine (TCM) offers as a promising candidate to treat pathological scars. A large number of TCMs have been studied to show anti-scarring effect, however, the natural barrier of the skin impedes their penetration, lowering its therapeutic efficacy. Herein, we reported the use of dissolvable hyaluronic acid (HA) microneedles (MNs) as a vehicle to aid the transdermal delivery of therapeutic agent, a model TCM called shikonin for the treatment of hypertrophic scars. Here, shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration, making its dosage controllable during the fabrication process. The therapeutic effect of the shikonin HA MNs was studied in vitro using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction. Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes (i.e., TGFβ1, FAP-α and COL1A1). Furthermore, we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.Agency for Science, Technology and Research (A*STAR)Published versionChenjie Xu acknowledges the funding support from SingaporeAgency for Science, Technology and Research (A)STAR) Sci-ence and Engineering Research Council Additive Manufacturingfor Biological Materials (AMBM) program (A18A8b0059,Singapore), City University of Hong Kong (#9610472, China),General Research Fund (GRF) from University Grant Committeeof Hong Kong (UGC) Research Grant Council (RGC) (#9042951,China), and NSFC/RGC Joint Research Scheme (N_CityU118/20,China)

Ocular Delivery of Predatory Bacteria with Cryomicroneedles Against Eye Infection

10.1002/advs.202102327Advanced Science821210232

In situ generation of zinc oxide nanobushes on microneedles as antibacterial coating

This paper introduces a facile and scalable method to generate a layer of antibacterial coating on microneedles. The antibacterial coating (i.e., zinc oxide nanobushes) is generated on the surface of gold-coated polystyrene microneedles using the hydrothermal growth method. The antimicrobial property is examined using the agar diffusion test with both gram-positive and gram-negative bacteria.Agency for Science, Technology and Research (A*STAR)Accepted versionThe authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Singapore A*STAR Biomedical Research Council (IAF-PP grant), NTU SUG (M4082114), and the Primary Research & Development Plan of Jiangsu Province of China (BE2016770). The thermal evaporator was supported by the Center for Disruptive Photonic Technologies of NTU

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially