Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma.

Despite its established anti-diabetic activity, Metformin hydrochloride (MET) has been repurposed for the management of hepatocellular carcinoma (HCC). Owing to MET high aqueous solubility and poor oral permeability, a novel nanoplatform is sought to overcome the current challenges of traditional formulations. In this study, we developed MET-bridged nanocochleates (MET-CO) using a direct bridging method followed by optimization and assessment using various in-vitro and in-vivo pharmacokinetic methods.

A Modified Cell-Penetrating Peptide Enhances Insulin and Oxytocin Delivery across an RPMI 2650 Nasal Epithelial Cell Barrier In Vitro.

Unlabelled: Peptide-based treatments represent an expanding area and require innovative approaches to enhance bioavailability. Combination with cell-penetrating peptides (CPPs) is an attractive strategy to improve non-invasive delivery across nasal epithelial barriers for systemic and direct nose-to-brain transport. We previously developed a modified CPP system termed Glycosaminoglycan-binding Enhanced Transduction (GET) that improves insulin delivery across gastrointestinal epithelium.

Effects of Microenvironment and Dosing on Efficiency of Enhanced Cell Penetrating Peptide Nonviral Gene Delivery.

Transfection, defined as functional delivery of cell-internalized nucleic acids, is dependent on many factors linked to formulation, vector, cell type, and microenvironmental culture conditions. We previously developed a technology termed glycosaminoglycan (GAG)-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding peptides and cell penetrating peptides (CPPs) in the form of nanoparticles, using conventional cell culture. Herein, we demonstrate that the most simple GET transfection formulation (employing the FLR peptide) is relatively poor at transfecting cells at increasingly lower dosages.

Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment.

Invasive pulmonary aspergillosis (IPA) is the most devastating Aspergillus-related lung disease. Voriconazole (VRZ) is the first-line treatment against IPA. Despite availability in oral and parenteral dosage forms, risks of systemic toxicity dictate alternative pulmonary administration.

Bioinspired 3D-printed scaffold embedding DDAB-nano ZnO/nanofibrous microspheres for regenerative diabetic wound healing.

There is a constant demand for novel materials/biomedical devices to accelerate the healing of hard-to-heal wounds. Herein, an innovative 3D-printed bioinspired construct was developed as an antibacterial/regenerative scaffold for diabetic wound healing. Hyaluronic/chitosan (HA/CS) ink was used to fabricate a bilayer scaffold comprising a dense plain hydrogel layer topping an antibacterial/regenerative nanofibrous layer obtained by incorporating the hydrogel with polylactic acid nanofibrous microspheres (MS).

Orally-delivered insulin-peptide nanocomplexes enhance transcytosis from cellular depots and improve diabetic blood glucose control.

Insulin regulates blood glucose levels, and is the mainstay for the treatment of type-1 diabetes and type-2 when other drugs provide inadequate control. Therefore, effective oral Insulin delivery would be a significant advance in drug delivery. Herein, we report the use of the modified cell penetrating peptide (CPP) platform, Glycosaminoglycan-(GAG)-binding-enhanced-transduction (GET), as an efficacious transepithelial delivery vector in vitro and to mediate oral Insulin activity in diabetic animals.

Nano zinc oxide-functionalized nanofibrous microspheres: A bioactive hybrid platform with antimicrobial, regenerative and hemostatic activities.

Bioactive hybrid constructs are at the cutting edge of innovative biomaterials. PLA nanofibrous microspheres (NF-MS) were functionalized with zinc oxide nanoparticles (nZnO) and DDAB-modified nZnO (D-nZnO) for developing inorganic/nano-microparticulate hybrid constructs (nZnO@NF-MS and D-nZnO@NF-MS) merging antibacterial, regenerative, and haemostatic functionalities. The hybrids appeared as three-dimensional NF-MS frameworks made-up entirely of interconnecting nanofibers embedding nZnO or D-nZnO.

Direct contact-mediated non-viral gene therapy using thermo-sensitive hydrogel-coated dressings.

Nanotechnologies are being increasingly applied as systems for peptide and nucleic acid macromolecule drug delivery. However systemic targeting of these, or efficient topical and localized delivery remains an issue. A controlled release system that can be patterned and locally administered such as topically to accessible tissue (skin, eye, intestine) would therefore be transformative in realizing the potential of such strategies.

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells.

Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells, and multiple bioactivities offer promise as drug carriers for colon targeting. Our objective was to evaluate LAGs functionalized with prodigiosin (PG), apoptotic secondary bacterial metabolite, as a bioinspired formulation against colorectal cancer (CRC). LAGs were prepared by a chemical method and highly purified by density gradient centrifugation.

Enhanced oral permeability of Trans-Resveratrol using nanocochleates for boosting anticancer efficacy; in-vitro and ex-vivo appraisal.

Hepatocellular carcinoma (HCC) is a prevalent liver cancer representing the fourth most lethal cancer worldwide. Trans-Resveratrol (T-R) possesses a promising anticancer activity against HCC. However, it suffers from poor bioavailability because of the low solubility, chemical instability, and hepatic metabolism.

3D printed bioinspired scaffolds integrating doxycycline nanoparticles: Customizable implants for in vivo osteoregeneration.

3D printing has revolutionized pharmaceutical research, with applications encompassing tissue regeneration and drug delivery. Adopting 3D printing for pharmaceutical drug delivery personalization via nanoparticle-reinforced hydrogel scaffolds promises great regenerative potential. Herein, we engineered novel core/shell, bio-inspired, drug-loaded polymeric hydrogel scaffolds for pharmaceutically personalized drug delivery and superior osteoregeneration.

3D bioprinting of a stem cell-laden, multi-material tubular composite: An approach for spinal cord repair.

Development of a biomimetic tubular scaffold capable of recreating developmental neurogenesis using pluripotent stem cells offers a novel strategy for the repair of spinal cord tissues. Recent advances in 3D printing technology have facilitated biofabrication of complex biomimetic environments by precisely controlling the 3D arrangement of various acellular and cellular components (biomaterials, cells and growth factors). Here, we present a 3D printing method to fabricate a complex, patterned and embryoid body (EB)-laden tubular scaffold composed of polycaprolactone (PCL) and hydrogel (alginate or gelatine methacrylate (GelMA)).

Hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles for enhanced osteogenesis.

Hydroxyapatite nanoparticles (HApN) are largely employed as osteogenic inorganic material. Inorganic/polymeric hybrid nanostructures can provide versatile bioactivity for superior osteogenicity, particularly as nanoparticles. Herein, we present hybrid biomaterial-based hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) realized using simple preparation techniques to augment HApN osteogenicity.

Antibiotic-free combinational hyaluronic acid blend nanofibers for wound healing enhancement.

An innovative approach in the functionalization of nanofibers (NFs) for wound healing relies on non-antibiotic combinational therapy to subdue microbial invasion while reducing antimicrobial resistance and enhancing healing. Despite great potentials, wound healing efficacy of NFs embedding antimicrobial metal nanoparticles (NPs)/essential oils has been scarcely documented. We developed combinational NFs using an electrospinnable hyaluronic acid/polyvinyl alcohol/polyethylene oxide blend embedding a new ZnO NPs/cinnamon essential oil (CEO) antimicrobial combination.

Human-scale tissues with patterned vascular networks by additive manufacturing of sacrificial sugar-protein composites.

Combating necrosis, by supplying nutrients and removing waste, presents the major challenge for engineering large three-dimensional (3D) tissues. Previous elegant work used 3D printing with carbohydrate glass as a cytocompatible sacrificial template to create complex engineered tissues with vascular networks (Miller et al. 2012, Nature Materials).

Highly efficient intracellular transduction in three-dimensional gradients for programming cell fate.

Unlabelled: Fundamental behaviour such as cell fate, growth and death are mediated through the control of key genetic transcriptional regulators. These regulators are activated or repressed by the integration of multiple signalling molecules in spatio-temporal gradients. Engineering these gradients is complex but considered key in controlling tissue formation in regenerative medicine approaches.