Controlled Release of Lysozyme Using Polyvinyl Alcohol-Based Polymeric Nanofibers Generated by Electrospinning.

Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics. LZM-loaded PVA monolithic nanofibers having 50% drug content exhibit efficient entrapment, wherein rapid dissolution is achieved within 30 min. The initial burst of LZM from the nanofiber was reduced as the LZM content was lowered. The initial dissolution is greatly influenced by the choice of PVA grade used; fully hydrolyzed PVA nanofibers demonstrate controlled release due to the reduced water solubility of PVA. Furthermore, coaxial electrospinning, which creates core-shell nanofibers with polycaprolactone as a controlled release layer, enables sustained LZM release over an extended period. This study confirms a correlation between PVA characteristics and controlled drug release and provides valuable insights into tailoring nanofiber properties for pharmaceutical applications.

Dry Powder Inhalers for Proteins Using Cryo-Milled Electrospun Polyvinyl Alcohol Nanofiber Mats.

To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the preparation processes, may result in the degradation and denaturation of drugs such as those based on peptides and proteins. Here, we showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. The cryo-milled nanofiber mats were porous to fine particles, and the particle size and drug stability depended on the freezing and milling times. The median diameter of the milled fiber mats was 12.6 µm, whereas the mass median aerodynamic diameter was 5.9 µm. The milled nanofiber mats were successfully prepared, while retaining the enzymatic activity of α-chymotrypsin; furthermore, the activity of milled fiber mats that had been stored for 6 months was comparable to the activity of those that were freshly prepared. This novel method may be suitable for the DPI preparation of various drugs because it avoids the heating step during the DPI preparation process.

Oral mucus-penetrating PEGylated liposomes to improve drug absorption: Differences in the interaction mechanisms of a mucoadhesive liposome.

We investigated the feasibility of densely polyethylene glycol (PEG2000)-modified liposomes as mucus-penetrating particles (MPPs) for oral delivery of systemically absorbed peptides. The oral absorption of MPPs and mucoadhesive liposomes modified with glycol chitosan (GCS) was compared. In an in vitro artificial mucus model, the densely PEGylated liposomes showed mucus permeability. Intracellular uptake of liposomes was evaluated in a Caco-2 and mucus-secreting Caco-2/HT29 co-culture. Intracellular uptake of MPPs was unaffected by mucus in the co-culture system, whereas the cellular uptake of GCS-liposomes was lower with a mucus layer than in Caco-2 alone. Rat in vivo oral absorption of liposomes was evaluated by using fluorescein isothiocyanate dextran (FD) as a model peptide drug. Oral absorption was higher for densely PEGylated than for unmodified liposomes and was PEG-concentration dependent, but excessive PEGylation decreased FD blood concentration. PEGylated liposomes incorporating spermine (SPM) as an absorption enhancer were then designed and showed the highest in vivo absorption of FD of all tested formulations. The pharmacological effects of the oral liposomes were evaluated by using elcatonin and did not correlate with FD oral absorption. The non-PEGylated SPM liposomes showed the highest pharmacological effect, suggesting the need for drug-specific optimization of liposomal components and surface modifiers.