Development of an Insulin Nano-Delivery System through Buccal Administration

Aim: To develop a new nano-delivery system for insulin buccal administration. Background: Biodegradable polymeric nanoparticles (PNPs) had viewed countless breakthroughs in drug delivery systems. The main objective of PNPs application in delivering and carrying different promising drugs is to make sure that the drugs being delivered to their action sites. As a result maximizing the desired effect and overcoming their limitations and drawbacks. Objectives: The main goals of this study were to produce an insulin consumable nano-delivery system for buccal administration and enhance the mucoadhesive effect in sustaining insulin release. Methods: Water in oil in water (W-O-W) microemulsion solvent evaporation technique was used for the preparation of nanoparticles consisting from positively charged poly (D, L-lactide-co-glycolide) coated with chitosan and loaded with insulin. Later, a consumable buccal film was prepared by the spin coating method and loaded with the previously prepared nanoparticles. Results: The newly prepared nanoparticle was assessed in terms of size, charge and surface morphology using a Scanning Electron Microscope (SEM), zeta potential, Atomic Force Microscope (AFM), and Fourier Transform Infra-red (FTIR) spectroscopy. An in-vitro investigation of the insulin release, from nanoparticles and buccal film, demonstrated controlled as well as sustained delivery over 6 hrs. The cumulative insulin release decreased to about (28.9%) with buccal film in comparing with the nanoparticle (50 %). Conclusion: The buccal film added another barrier for insulin release. Therefore, the release was sustained.

Mapping evidence on strengthened and sustained delivery early detection and management of Hypertension and Diabetes among PLWH: a scoping review protocol

The full text of this preprint has been withdrawn by the authors while they make corrections to the work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

Sustained Delivery of Lactoferrin Using Poloxamer Gels for Local Bone Regeneration in a Rat Calvarial Defect Model

Lactoferrin (LF) is a multifunctional milk glycoprotein that promotes bone regeneration. Local delivery of LF at the bone defect site is a promising approach for enhancement of bone regeneration, but efficient systems for sustained local delivery are still largely missing. The aim of this study was to investigate the potential of the poloxamers for sustained delivery of LF to enhance local bone regeneration. The developed LF/poloxamer formulations were liquid at room temperature (20 °C) transforming to a sustained releasing gel depot at body temperature (37 °C). In vitro release studies demonstrated an initial burst release (~50%), followed by slower release of LF for up to 72 h. Poloxamer, with and without LF, increased osteoblast viability at 72 h (p < 0.05) compared to control, and the immune response from THP-1 cells was mild when compared to the suture material. In rat calvarial defects, the LF/poloxamer group had lower bone volume than the controls (p = 0.0435). No difference was observed in tissue mineral density and lower bone defect coverage scores (p = 0.0267) at 12 weeks after surgery. In conclusion, LF/poloxamer formulations support cell viability and do not induce an unfavourable immune response; however, LF delivery via the current formulation of LF200/poloxamer gel did not demonstrate enhanced bone regeneration and was not compatible with the rat calvarial defect model.

Sulfated Hydrogels in Intervertebral Disc and Cartilage Research

Hydrogels are commonly used for the 3D culture of musculoskeletal cells. Sulfated hydrogels, which have seen a growing interest over the past years, provide a microenvironment that help maintain the phenotype of chondrocytes and chondrocyte-like cells and can be used for sustained delivery of growth factors and other drugs. Sulfated hydrogels are hence valuable tools to improve cartilage and intervertebral disc tissue engineering. To further advance the utilization of these hydrogels, we identify and summarize the current knowledge about different sulfated hydrogels, highlight their beneficial effects in cartilage and disc research, and review the biofabrication processes most suitable to secure best quality assurance through deposition fidelity, repeatability, and attainment of biocompatible morphologies.

Injectable in situ gelling delivery system for the treatment of jawbone infections

Aim: A polymeric in situ gelling delivery system for localized and sustained delivery to jawbone infections was developed. Materials & methods: In situ gelling delivery systems were prepared using either poly-dl-lactic acid or chitosan and Pluronic F127/Pluronic F68. Metronidazole nanoparticles were prepared using poly (dl-lactide-co-glycolide) or chitosan. Poly (dl-lactide-co-glycolide) was used for microparticles. Particles were characterized for size, charge and morphology. Results: Viscosity and yield stress of the gels were 0.4 Pa.s and 2 Pa, respectively, with 70% cell viability over 72 h. Around 90% of loaded metronidazole was released at a sustained rate over 1 week. Conclusion: Use of appropriate amount of nano/microparticles in the gel resulted in a sustained release over a period of 1 week – needed for jawbone infection.

Polymer nanofibers for biomedical applications: advances by electrospinning

Background: The demand for novel biomaterials has been exponentially rising in the last years as well as the searching for new technologies able to produce more efficient products in both drug delivery systems and regenerative medicine. Objective: The technique that can pretty well encompass the needs for novel and high-end materials with a relatively low-cost and easy operation is the electrospinning of polymer solutions. Methods: Electrospinning usually produces ultrathin fibers that can be applied in a myriad of biomedical devices including sustained delivery systems for drugs, proteins, biomolecules, hormones, etc that can be applied in a broad spectrum of applications, from transdermal patches to cancer-related drugs. Results: Electrospun fibers can be produced to mimic certain tissues of the human body, being an option to create new scaffolds for implants with several advantages. Conclusions: In this review, we aimed to encompass the use of electrospun fibers in the field of biomedical devices, more specifically in the use of electrospun nanofibers applications toward the production of drug delivery systems and scaffolds for tissue regeneration.

Localized delivery of β-NGF via injectable microrods accelerates endochondral fracture repair

Currently, there are no biological approaches to accelerate bone fracture repair. Osteobiologics that promote endochondral ossification are an exciting alternative to surgically implanted bone grafts, however, the translation of osteobiologics remains elusive because of the need for localized and sustained delivery that is both safe and effective. In this regard, an injectable system composed of hydrogel-based microparticles designed to release osteobiologics in a controlled and localized manner is ideal in the context of bone fracture repair. Here, we describe poly (ethylene glycol) dimethacrylate (PEGDMA)-based microparticles, in the form of microrods, engineered to be loaded with beta nerve growth factor (β-NGF) for use in a murine tibial fracture model. In-vitro studies demonstrated that protein-loading efficiency is readily altered by varying PEGDMA macromer concentration and that β-NGF loaded onto PEGDMA microrods exhibited sustained release over a period of 7 days. In-vitro bioactivity of β-NGF was confirmed using a tyrosine receptor kinase A (Trk-A) expressing cell line, TF-1. Moreover, TF-1 cell proliferation significantly increased when incubated with β-NGF loaded PEGDMA microrods versus β-NGF in media. In-vivo studies show that PEGDMA microrods injected into the fracture calluses of mice remained in the callus for over 7 days. Importantly, a single injection of β-NGF-loaded PEGDMA microrods resulted in significantly improved fracture healing as indicated by significant increases in bone volume, trabecular connective density, and bone mineral density and a significant decrease in cartilage despite a remarkably lower dose (~111 fold) than the β-NGF in media. In conclusion, we demonstrate a novel and translational method of delivering β-NGF via injectable PEGDMA microrods to improve bone fracture repair.

Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles

Synthetic and naturally occurring nano-sized particles present versatile vehicles for the delivery of therapy in a range of clinical settings. Their small size and modifiable physicochemical properties support refinement of targeting capabilities, immune response, and therapeutic cargo, but rapid clearance from the body and limited efficacy remain a major challenge. This highlights the need for a local sustained delivery system for nanoparticles (NPs) and extracellular vesicles (EVs) at the target site that will ensure prolonged exposure, maximum efficacy and dose, and minimal toxicity. Biocompatible hydrogels loaded with therapeutic NPs/EVs hold immense promise as cell-free sustained and targeted delivery systems in a range of disease settings. These bioscaffolds ensure retention of the nano-sized particles at the target site and can also act as controlled release systems for therapeutics over a prolonged period of time. The encapsulation of stimuli sensitive components into hydrogels supports the release of the content on-demand. In this review, we highlight the prospect of the sustained and prolonged delivery of these nano-sized therapeutic entities from hydrogels for broad applications spanning tissue regeneration and cancer treatment. Further understanding of the parameters controlling the release rate of these particles and efficient transfer of cargo to target cells will be fundamental to success.