Medicated Nanofibers: Production and Advantages

Introduction to Medicated Nanofibers

• Modern polymeric drug delivery systems are made to release drugs consistently to diseased skin areas.
• Polymeric nanofibers are now used as efficient topical drug delivery systems.
• Nanofibers are very thin, hollow, polymeric filaments.
• Nanofibers' diameters range from 50 to 500 nanometers.

Advantages of Nanofibers

• Nanofibers have a high porosity allowing for a high percentage of drug loading.
• Multiple drugs can be loaded on one nanofiber mat or platform.
• Nanofibers enhance drug dissolution due to their large surface area and surface area-to-volume ratio.
• They provide varied drug release patterns.
• Different pore sizes allow for loading of particulate matters and drugs with high molecular weights.
• They can be administered through multiple routes.

Electrospinning

• Electrospinning is a technique used to produce nanofibers.
• It is cost-effective, requires simple tooling, and produces ultrafine fibers for drug delivery.
• The technique relies on the effect of electric current on fluid dynamics.
• Droplets of polymer solution are forced through a metallic needle towards a metallic collector.
• The needle and collector are connected to a high voltage, from 1 to 30 kV.
• This voltage overcomes the surface tension of the polymer solution.
• The charged polymer droplet forms a Taylor cone at the needle tip and is ejected towards the collector.
• As the polymer solution accelerates, the solvent evaporates and nanofibers are collected on the collector's surface.

Factors Influencing Nanofiber Formation

Polymer Solution Parameters

• Ideal polymers for nanofiber drug carriers are biocompatible, biodegradable, non-toxic, moderately hydrophilic, and have appropriate mechanical strength.
• Nanofibers can be made from a single polymer or a blend of polymers that can be natural or synthetic.
• Composite nanofibers have optimal biological properties and mechanical strength from natural and synthetic polymers, respectively.
• Water is the most commonly used solvent due to its safety and biocompatibility, but its use is limited to hydrophilic polymers.
• Organic solvents pose challenges due to toxicity, cost, and volatility.
• A combination of solvents is often used to optimize solution viscosity, surface tension, and solvent volatility.
• High molecular weight polymers are preferable for electrospinning because they enable sufficient intermolecular entanglements.
• Low molecular weight polymers and those with polyelectrolytic nature are challenging to electrospin.
• Increasing polymer concentration raises solution viscosity, which results in more uniform nanofibers, but with higher fiber diameters.
• Lower surface tension values typically yield fibers without beads, allowing for the use of lower voltages during electrospinning; surface tension can be influenced by adding surfactants.
• Polymer solutions with low conductivity cannot be electrospun due to the lack of surface charge required for Taylor cone formation.
• Higher conductivities generally result in thinner nanofibers, and low conductivity can be solved by adding salts to uncharged polymers.

Process Parameters

• Solutions with low conductivity, high surface tension, and high viscosity require higher voltages, leading to thinner fibers.
• The distance between the needle tip and the collector influences nanofiber size and morphology.
• Increased distances typically result in thinner fibers.
• When the flow rate of the solution increases, thicker nanofibers are formed due to the formulation of a thicker jet.
• A conductive flat collector produces randomly oriented nanofiber mats, while a rotating metallic cylindrical collector yields aligned nanofibers.

Ambient Parameters

• Environmental temperature and relative humidity are the ambient parameters affecting nanofiber formation.
• Higher environmental temperatures increase solvent evaporation rates, resulting in thicker nanofibers.
• For hydrophobic polymers dissolved in organic solvents, higher relative humidity leads to more porous nanofibers.
• In aqueous polymer solutions, low relative humidity causes rapid solvent evaporation, resulting in thicker nanofiber formation.

Nanofiber Drug Loading Techniques

• There are four main techniques for loading electrospun nanofibers with drugs, and the method chosen impacts the structure and drug release pattern of the nanofiber mats.
• Immobilizing after electrospinning: a plain nanofiber mat is prepared and immersed in a drug solution, causing the drug to conjugate with the polymer molecules.
  • This leads to a fast initial release from the surface, followed by a sustained diffusion-controlled release.
• Blend electrospinning: the drug is dissolved directly into the polymer solution, embedding it within the produced nanofiber.
  • This requires the drug and polymer to be soluble in the same solvent.
• Emulsion electrospinning: the drug and polymer are dissolved in immiscible solvents.
  • The two solutions are blended with an emulsifying agent to form an emulsion that can be electrospun.
  • The drug is encapsulated in the polymeric matrix, showing sustained release as the release needs formation of pores in the outer sheath and dissolution of the polymer surrounding the drug
• Coaxial electrospinning: simultaneous electrospinning of two immiscible polymer solutions containing drugs in the core and sheath.
  • A coaxial needle arrangement separates the solutions, with one pumped through the outer needle and the other through the inner needle.
  • Drug release requires dissolution of the core polymer and pore formation in the shell polymer, resulting in sustained drug release.