Photocurable poly(ethylene glycol) as a bioink for the inkjet 3D pharming of hydrophobic drugs.

Binder jetting and material extrusion are the two most common additive manufacturing techniques used to create pharmaceutical tablets. However, their versatility is limited since the powder component is present throughout the dosage forms fabricated by binder jet 3D printing and material extrusion 3D printing requires high operating temperatures. Conversely, material jetting allows for compositional control at a voxel level and can dispense material at room temperature. Unfortunately, there are a limited number of materials that are both printable and biocompatible. Therefore, the aim of this study was to engineer photocurable bioinks that are suitable for hydrophobic active pharmaceutical ingredients and have rapid gelation times upon visible light exposure. The resulting bioinks were comprised of poly(ethylene glycol) diacrylate (250 Da) as the crosslinkable monomer, Eosin Y as the photoinitiator, and methoxide-poly(ethylene glycol)-amine as the coinitiator. Additionally, poly(ethylene glycol) (200 Da) was added as a plasticizer to modulate the drug release profiles, and Naproxen was used as the model drug due to its high hydrophobicity. Various bioink formulations were dispensed into the bottom half of blank preform tablets - made via direct compression - using a piezoelectric nozzle, photopolymerized, and capped with the top half of the preform tablet to complete the pharmaceutical dosage form. Results from the release studies showed that drug release can be modulated by both the percent of poly(ethylene glycol) diacrylate in the formulation and the light exposure time used to cure the bioinks. These bioinks have the potential to expand the library of materials available for creating pharmaceutical tablets via inkjet printing with personalized drug dosages.

Photocurable Bioinks for the 3D Pharming of Combination Therapies.

Combination therapies mediate drug synergy to improve treatment efficacy and convenience, leading to higher levels of compliance. However, there are challenges with their manufacturing as well as reduced flexibility in dosing options. This study reports on the design and characterization of a polypill fabricated through the combination of material jetting and binder jetting for the treatment of hypertension. The drugs lisinopril and spironolactone were loaded into hydrophilic hyaluronic acid and hydrophobic poly(ethylene glycol) (PEG) photocurable bioinks, respectively, and dispensed through a piezoelectric nozzle onto a blank preform tablet composed of two attachable compartments fabricated via binder jetting 3D printing. The bioinks were photopolymerized and their mechanical properties were assessed via Instron testing. Scanning electron microscopy (SEM) was performed to indicate morphological analysis. The polypill was ensembled and drug release analysis was performed. Droplet formation of bioinks loaded with hydrophilic and hydrophobic active pharmaceutical ingredients (APIs) was achieved and subsequently polymerized after a controlled dosage was dispensed onto preform tablet compartments. High-performance liquid chromatography (HPLC) analysis showed sustained release profiles for each of the loaded compounds. This study confirms the potential of material jetting in conjunction with binder jetting techniques (powder-bed 3D printing), for the production of combination therapy oral dosage forms involving both hydrophilic and hydrophobic drugs.

Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis.

Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1(G93A)). Treating symptomatic SOD1(G93A) mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1(G93A) mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1(G93A) mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1(G93A) mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1(G93A) mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS.