advantages in targeted gene delivery to the posterior eye, thus limiting the use of

multiple invasive injections. Luxturna (voretigene neparvovec-rzyl) is a FDA

approved Adeno Associated Virus (AAV) gene therapy to treat eye disorders in

humans (Smalley 2017). Moreover, there are a number of other clinical trials going

on around the

world

to treat

eye diseases

through

gene

therapy using

magnetofection (Bordet and Behar-Cohen 2019; Czugala et al. 2016).

17.3.2.3 Gastrointestinal Tract

Recently, we have demonstrated successful delivery of microRNA-139-5p

(miR-139-5p) into the rat internal anal sphincter (IAS) (Singh et al. 2018) using

in vivo magnetofection. The IAS tone plays a major role in the rectoanal continence

via activation of RhoA-associated kinase (ROCK2), miR-139-5p targeting Rho

kinase 2 (Singh et al. 2017). Using a multi-pronged approach of confocal micros-

copy showing confined delivery of miRNA around IAS through immunofluores-

cence images as well as ex vivo physiological and biochemical validation showing

that miR-139-5p decreased the basal IASP (internal anal sphincter pressure), the

basal IAS tone, and the rates of contraction and relaxation which are associated with

fecal pellet output, we demonstrated that magnetofection is a novel method of

in vivo gene delivery for the site-directed therapy of the rectoanal motility disorders.

These studies have direct therapeutic implications in rectoanal motility disorders

especially associated with IAS (Fig. 17.5) and potentially other gastrointestinal

motility disorders.

Another group of researchers have reported the potential usage of magnetofection

for in vivo delivery of silencer RNA (siRNA) using magnetic crystal-lipid

nanostructures in cancer gene therapy (Namiki et al. 2009). Authors here used a

magnetite nanocrystal coated with oleic acid and a cationic lipid shell and

complexed it to EGFR-specific siRNA, which was injected to the mice. Following

administration of siRNA complexed to the magnetic core-encapsulated cationic lipid

shell, authors observed the distribution in the spleen followed by the liver and lung.

For in vivo magnetofection, titanium nitride-coated magnets were internally

implanted under the skin peripheral to tumor lesions or were externally placed

onto the skin. Authors observed a significant reduction in tumor volume compared

to the control group following internal and external applications of a magnetic field

28 days after the initiation of treatment.

17.3.3 Magnetic Implants

While stationary external magnets are useful in superficial drug delivery under the

skin, it can be challenging to deliver drugs into the deeper layers of the skin and

internal tissues. Here, use of magnetic implants deep under the skin and deep in the

body shows a promising solution (Shapiro 2009). Ge et al. provided a proof of

concept for the magnetic implant-directed nanodrug delivery substituting the need

for an external magnetic field (Ge et al. 2017). They used a biocompatible magnetic

implant scaffold made of a magnetite/poly (lactic-co-glycolic acid) nanocomposite

310

J. Singh et al.