비만아 부모의 돌봄 경험: q 방법론

In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine.

/pdf/opportunities-and-challenges-in-the-delivery-of-mrna-based-1a0iktzvi4.pdf

Opportunities and Challenges in the Delivery of mRNA-based Vaccines.

Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1-55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.

Biodegradable 3D printed polymer microneedles for transdermal drug delivery.

Recent advances of microneedles for biomedical applications: drug delivery and beyond.

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability

3D printed drug delivery and testing systems - a passing fad or the future?

The hand function of patients who suffer from trigger finger can be impaired by the use of traditional splints. There is also a risk of systemic side effects with oral non-steroidal anti-inflammatory drugs (NSAIDs) used for pain relief. Microneedle-assisted transdermal drug delivery offers an attractive alternative for local delivery of NSAIDs. However, traditional microneedle arrays fabricated on flat surfaces are unable to deliver drugs effectively across the undulating skin surface of affected finger(s). In this study, using 3D printing, a dual-function microneedle array has been fabricated on personalized curved surfaces (microneedle splint) for drug delivery and splinting of the affected finger. The novel microneedle splint was assessed for its physical characteristics and the microneedles were shown to withstand up to twice the average thumb force without fracturing. An average skin penetration efficiency of 64% on dermatomed human cadaver skin was achieved and the final microneedle splint showed biocompatibility with human dermal cell lines. A significantly higher amount of diclofenac permeated through the skin by 0.5 h with the use of the microneedle splint as compared to intact skin. The fabricated microneedle splint can thus be a potential new approach to treat trigger finger via personalized splinting without affecting normal hand function.

https://iopscience.iop.org/article/10.1088/1758-5090/9/1/015010/pdf

Three-dimensional printing of a microneedle array on personalized curved surfaces for dual-pronged treatment of trigger finger.

In this paper, we report a proof of concept study on the fabrication, characterization and therapeutic evaluation of in vitro transcribed messenger RNA (mRNA) loaded in a dissolving microneedle patch (RNApatch). We show that low molecular weight polyvinylpyrrolidone (PVP) can directly be used without further purification for RNApatch fabrication with no detectable mRNA degradation. Physical and functional integrity of mRNA stored within the RNApatch are completely preserved for at least 2 weeks under ambient conditions. While the loading of mRNA into RNApatch is limited by the solubility of mRNA in concentrated PVP solution, mechanical strength of RNApatch is not compromised by the presence of mRNA. RNApatch can mediate in vivo transgene expression of mRNA encoding luciferase for up to 72 hours and transfection efficiency and kinetics mediated by RNApatch compares favorably to subcutaneous injection. Interestingly, mRNA transfection efficiency does not correlate with contact surface area but instead increases with deeper delivery depths. In an E.G7-OVA immunotherapy model, RNApatch induces slightly higher cellular and humoral immune responses compared to subcutaneous injection. In conclusion, RNApatch is a viable delivery platform for mRNA and represents an attractive option with significant translation potential for the delivery of mRNA therapeutics.

/pdf/formulation-characterization-and-evaluation-of-mrna-loaded-34hrf2ikoi.pdf

Seng Han Lim

Papers

3D printed drug delivery and testing systems - a passing fad or the future?

Three-dimensional printing of a microneedle array on personalized curved surfaces for dual-pronged treatment of trigger finger.

Formulation, characterization and evaluation of mRNA-loaded dissolvable polymeric microneedles (RNApatch)

High resolution photopolymer for 3D printing of personalised microneedle for transdermal delivery of anti-wrinkle small peptide.

Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold