3P Electrohyrodynamic Printing For Customized Multi-drug Laoded Membranes

Multi-drug loaded fibrous membranes with well aligned 3D structures have wide potential applications in biomedical engineering fields.Electrohydrodynamic(EHD)three-dimension(3D)printing is a versatile rapid prototype technology,which can be used to manufacture various 3D structures by accumulating stacked layers,to satisfy different requirements.In this study,drug loaded 3D membranes were prepared via EHD 3D printing technique(or a combination of EHD 3D printing and electrospinning techniques).The precision control of the membrane properties,e.g.drug release property and mechanical property,can be achieved by regulatinging the designs of the membrane structures,to meet the demands of personalized medicineFirstly,complex fibrous multi-layered ibuprofen(IBU)-cellulose acetate(CA)composite films were designed and fabricated via EHD 3D printing.Effect of preparation parameter on fiber morphologies and depositions were analyzed in detail.Hydrophilic/hydrophobic components were encapsulated into composite films.Moreover,the drug release rates and mechanisms were varied with the change of the void geometry integration designs.Secondly,a flexible multi-drug loaded composite membrane was manufactured via EHD 3D printing.The composite membrane comprised three parts,including two different drug-loaded parts and a middle poly-ε-caprolactone(PCL)folding part.This composite membrane can be folded and embedded into normal capsules,and unfolding after oral administration,which can extend the gastrointestinal transit time and thus,improve drug bioavailability.The flexibility of the composite membrane can be controlled by changing the layer numbers of the middle folding part.Moreover,the composite membrane possessed extensive potential applications in drug combination therapy by altering the drug selections in drug-loaded partsFinally,a novel multi-drug loaded membrane sandwich with structures infused with ibiprofen(IBU)and ganoderma lucidum polysaccharide(GLP)were manufecturcd using a combination of electro hydrodynamic(EHD)3D printing and eleclrospinning(ES)techniques.The diameter distribution of printed fibers was 40～90μm,and the diameter distribution of electrospun fibers was 100～900 nm,The resulting membrane sandwich displayed a trihasic drug release profile that GLP immediately released after the capsule shell and the PVP were dissolved,followed by the short term quick release of 60%IBU within the first hour afterwards,and the remaining IBU showed a sustained release fitting a Fickian diffusion kinetics.This work demonstrated a method to prepare multi-drug oral systems with precisely patterned structures,which can be used for personalized therapeutic dosing control and customized patient therapy.