**7. Nanoparticle delivery systems**

The technique of iontophoresis has the potential to be expanded to deliver proteins and pep‐ tides. The current can be literally switched on and off and modified, also iontophoretic delivery enables rapid onset and offset, and drug delivery is highly controllable and programmable.

This transdermal drug delivery technique uses short electrical pulses of high voltage to create transient aqueous pores in the skin, in a variety of forms, temporarily to disrupt the stratum corneum and to allow drug in the reservoir or the polymeric matrix to cross the stratum cor‐

This transdermal drug delivery technique uses low‐frequency ultrasonic energy (15‐second burst of ultrasound at 55 kHz) to disrupt the stratum corneum and to allow drug in the reservoir or the polymeric matrix to cross the stratum corneum and then penetrate the blood vessel. Similar to the electroporation effect, the sound waves create cavitation bubbles in the tissue that disrupt the lipid bilayers of the cells of the stratum corneum creating microchan‐ nels. The ultrasound poration can increase the transport properties of the stratum corneum by

This transdermal patch technique makes use of microneedles, which are microscopic, just a few hundred microns in size. They can pierce the skin in a minimally invasive manner

**Figure 12.** Temporary disruption of the bilipid membrane after electroporation. A: Normal arrangement of the bilipid

membrane B: Bilipid membrane after electroporation C: Recovery of the Bilipid membrane after an interval.

**6.2. Electroporation**

24 Pain Relief - From Analgesics to Alternative Therapies

**6.3. Sonophoresis**

**6.4. Microneedle dermal patch**

neum and then penetrate the blood vessel (**Figure 12**).

100‐fold. **Figure 13** illustrates the effect of sonophoresis.

Nanoparticle systems as drug carriers may also play a very important role in the deliv‐ ery of analgesics. The advantages of nanoparticles used as drug carriers include fast action of the nano formulation, high product stability, good loading capacity, both hydrophilic and hydrophobic substances can be given together in the same formulation, and various routes of administration can be utilized [11]. Analgesics in nanoparticulate systems would be transported and released in a controlled manner at the target area, depending on the environmental conditions. Analgesic nanoparticulate can have the following advantages: reducing the dose of the drug, some specialty formulation may allow analgesic drugs that normally do not cross the blood brain barrier to penetrate into the brain where this can reduce the peripheral side effects by lowering the amount needed to act directly on the central nervous system. The development of the analgesic‐loaded nanoparticulate systems may represent a future challenge to achieve promising agents for regional drug delivery in pain management strategy.

Nanoparticles can also be solid or soft colloidal matrix‐like polymeric particles or lipids. They can be drug carrier system such as liposomes. Other drug delivery sys‐ tems are based on using nanoparticles composed of biodegradable polymers, this has been explained in the earlier subsection on polymeric drug delivery system [17]. These microparticles may consist of polymeric nanospheres in an oily reservoir or aqueous medium. It was shown in research that a numbers of analgesic drugs such as ibuprofen, flurbiprofen, and acetyl salicylic acid have been successfully delivered by entrapping in nanoparticles [18].
