Sustained controlled drug release is one of the prominent contributions for more successful treatment outcomes in the case of several diseases. However, the incorporation of hydrophilic drugs into nanofibers, a promising novel delivery system, and achieving a long-term sustained release still pose a challenging task. In this work we demonstrated a robust method of avoiding burst release of drugs and achieving a sustained drug release from 2 to 4 weeks using core-shell nanofibers with poly(methyl methacrylate) (PMMA) shell and monolithic poly(vinyl alcohol) (PVA) core or a novel type of core-shell nanofibers with blended (PVA and PMMA) core loaded with ciprofloxacin hydrochloride (CIP). It is also shown that, for core-shell nanofibers with monolithic core, drug release can be manipulated by varying flow rate of the core PVA solution, whereas for core-shell nanofibers with blended core, drug release can be manipulated by varying the ratios between PMMA and PVA in the core. During coaxial electrospinning, when the solvent from the core evaporates in concert with the solvent from the shell, the interconnected pores spanning the core and the shell are formed. The release process is found to be desorption-limited and agrees with the two-stage desorption model. Ciprofloxacin-loaded nanofiber mats developed in the present work could be potentially used as local drug delivery systems for treatment of several medical conditions, including periodontal disease and skin, bone, and joint infections.
Nanofibers represent an attractive novel drug delivery system for prolonged and controlled release. However, sustained release of hydrophilic drugs, like ciprofloxacin hydrochloride (CIP), from polymeric nanofibers is not an easy task. The present study investigates the effect of different hydrophobic polymers (PCL and PMMA) alone in monolithic nanofibers or with hydrophilic polymers (PVA, PEO, and chitosan) in blended nanofibers aiming to achieve sustained CIP release. CIP release from PCL nanofibers was 46% and from PMMA just 1.5% over 40 day period. Thus, PMMA holds great promise for modification of CIP release from blended nanofibers. PMMA blends with 10% PEO, PVA, or chitosan were used to electrospin nanofibers from solution in the mixture of acetic and formic acid. These nanofibers exhibited different drug-release profiles: PEO containing nanofiber mats demonstrated high burst effect, chitosan containing mats revealed very slow gradual release, and PVA containing mats yielded smaller burst effect with favorable sustained release. We have also shown that gradual sustain release of antibiotic like CIP can be additionally tuned over 18 days with various blend ratios of PMMA with PVA or chitosan reaching almost 100%. A mathematical model in agreement with the experimental observation revealed that the sustained CIP release from the blended nanofibers corresponded to the two-stage desorption process.
Periodontal disease is chronic inflammation of periodontal tissues resulting in formation of periodontal pockets, periodontal attachment loss and progressive destruction of the ligament and alveolar bone. This review gives an update on periodontal disease pathogenesis, which is important for the development of novel methods and delivery systems for its treatment. The available treatment approaches, including removal of dental plaque, modulation of the host inflammatory response, and regeneration of periodontal tissue, are reviewed and their drawbacks discussed. Furthermore the latest achievements involving development of nanomedicines, which represent a new approach to better treatment of periodontal disease, are highlighted. They enable local drug delivery to particular tissues, cells, or subcellular compartments in periodontal pockets, either to biofilm pathogens or host cells, as well as control the release of incorporated drugs, usually antibiotic or anti-inflammatory. Specific examples of the nanocarriers or nanomaterials such as liposomes, lipid and polymeric nanoparticles, nanocrystals, dendrimers, and nanofibers under development for the treatment of periodontal disease are also clearly reviewed. Nanofibers are of special interest as nanodelivery systems and scaffolds for the regeneration of periodontal tissue. Finally, the future outlook of novel therapeutic approaches involving nanodelivery systems in the treatment of periodontal disease is provided.
Lactic acid bacteria can have beneficial health effects and be used for the treatment of various diseases. However, there remains the challenge of encapsulating probiotics into delivery systems with a high viability and encapsulation efficacy. The electrospinning of bacteria is a novel and little-studied method, and further investigation of its promising potential is needed. Here, the morphology, zeta potential, hydrophobicity, average cell mass, and growth characteristics of nine different species of Lactobacillus and one of Lactococcus are characterized. The electrospinning of polymer solutions containing ~10 log colony forming units (CFU)/mL lactic acid bacteria enabled the successful incorporation of all bacterial species tested, from the smallest (0.74 µm; Lactococcus lactis) to the largest (10.82 µm; Lactobacillus delbrueckii ssp. bulgaricus), into poly(ethylene oxide) nanofibers with an average diameter of ~100 nm. All of these lactobacilli were viable after incorporation into nanofibers, with 0 to 3 log CFU/mg loss in viability, depending on the species. Viability correlated with the hydrophobicity and extreme length of lactic acid bacteria, whereas a horizonal or vertical electrospinning set-up did not have any role. Therefore, electrospinning represents a promising method for the incorporation of lactic acid bacteria into solid delivery systems, while drying the bacterial dispersion at the same time.
Alginate is a promising biocompatible and biodegradable polymer for production of nanofibers for drug delivery and tissue engineering. However, alginate is difficult to electrospin due to its polyelectrolyte nature. The aim was to improve the ‘electrospinability’ of alginate with addition of exceptionally high molecular weight poly(ethylene oxide) (PEO) as a co-polymer. The compositions of the polymer-blend solutions for electrospinning were varied for PEO molecular weight, total (alginate plus PEO) polymer concentration, and PEO proportion in the dry alginate–PEO polymer mix used. These were tested for rheology (viscosity, complex viscosity, storage and loss moduli) and conductivity, and the electrospun nanofibers were characterized by scanning electron microscopy. One-parameter-at-a-time approach and response surface methodology (RSM) were used to optimize the polymer-blend solution composition to obtain defined nanofibers. Both approaches revealed that the major influence on nanofiber formation and diameter were total polymer concentration and PEO proportion. These polymer-blend solutions of appropriate conductivity and viscosity enabled fine-tuning of nanofiber diameter. PEO molecular weight of 2–4 million Da greatly improved the electrospinnability of alginate, producing nanofibers with >85% alginate. This study shows that RSM can be used to design nanofibers with optimal alginate and co-polymer contents to provide efficient scaffold material for regenerative medicine.
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