Miscellaneous Applications

Normally, drug delivery for cardiovascular diseases, like atherosclerosis, is less effective due to the poor drug transport through the walls of cardiac muscles. Choi et al. designed microneedles consisting of curved backing layers; these microneedles could wrap around the blood vessel in such a way that the tips of the microneedles were inserted into the tunica adventitia. To fabricate microneedles on a curved surface, discrete thermal drawing and postannealing processes are employed, which help the microneedles to enter the target vascular tissue and release the drug [164].

Microneedles can be used for needle-free delivery of anesthetics. As they are minimally invasive in nature, cause no pain, and are small in size (100 microns), they play a major role in drug delivery. Microneedle administration of anesthetics is identical to one injection of hypodermic needles. During drug delivery the sensitivity and concentration of the anesthetic given to the patient depend on the number and spacing of microneedles in the microneedle patch. Lidocaine is used as a drug for local anesthesia. Baek et al. showed consistent and higher delivery within 2 min by microneedle tips coated with lidocaine. Thus the proposed technique can be employed for painless and faster local anesthesia [165].

Baek et al. developed phenylephrine (PE) microneedles that help to increase PE availability to the anal sphincter, which is an effective treatment for fecal incontinence. The microneedles fabricated by using PE, which is used to increase perianal skin permeability for locally targeted drug delivery, help to increase resistance to anal sphincter pressure to treat fecal incontinence. The microneedle patches were developed by micromolding PLA [166].

Chiu et al. designed a microneedle with a cylindrical roller that allows rapid drug diffusion into the nail. The polymeric NPs act as drug reservoirs for sustained topical drug delivery into microneedle- treated human nail [167].

Thermoresponsive polymers [11] promote in situ gel formation, which helps in the sustainable delivery of a drug without any surgery during its application. Among the poloxamers or pluron- ics, a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer, representing a series of central chains of polyoxypropy- lene and two identical lateral hydrophilic chains of polyoxyethylene, has seen tremendous success in in situ carrier formation. These copolymers have a sol-gel transition behavior in an aqueous medium, reacting to the temperature change at skin (32°C) and body temperature (37°C). At room temperature (<30°C], the aqueous solutions are in a sol state; however, at certain temperatures (>lower critical solution temperature, 32°C] and concentrations, the gel transforms into a liquid form [168].

To treat restenosis, solid microneedles were applied across the internal elastic lamina of rabbit arteries ex vivo. To aid tissue engineering, hollow microneedles were developed to improve cell viability in slices of harvested brain tissue. These systems unlock many pathways for neurobiological and other culture systems [169].

Microneedles are extensively used in drug delivery to the skin, but they can also be used in diagnosis for extraction of analytes from the skin. As in one instance, a few microliters of interstitial fluid were sucked from skin pretreated with microneedles. The concentration of glucose present in the interstitial fluid was coherent with the BG levels in rats and human subjects [170, 171]. For monitoring glucose levels, several integrated diagnostic systems were developed involving microneedles with microactuators, microfluidic controls, and sensors. This system collects blood from the skin [172,173].

Microneedles also work as bioelectrical interfaces, especially for recording neural activity, stimulation [174-177], electrocardiography, and electroencephalography measurements [178,179].

Further, microneedle arrays have been upgraded to directly deliver drugs in an intracellular manner. In this approach DNA-coated microneedles transfected nematode cells while the nematode cells moved across the DNA-coated microneedle array. The microneedles pierced the nematode cuticle [180].

Wang et al. found that the vaginal mucosa may be a useful site for vaccination, specifically for targeted delivery of APCs to the vaginal tissue. Their group fabricated microneedle patches with ammonium bicarbonate-loaded multifunctional liposomes for vaginal mucosal vaccine adjuvant-dual delivery system and administered antigen using microneedle patches into the vaginal cavity. It is found to trigger a vigorous antigen-specific immune response systemically in the reproductive tract mucosa [181].

Bhatnagar et al. delivered chemotherapeutic agents such as tamoxifen and gemcitabine through microneedles for breast cancer treatment. Zein microneedles were developed using the micromolding technique containing 36 microneedles in a 1 cm2 area. These microneedles were loaded with two anti-breast cancer drugs, tamoxifen and gemcitabine, with different water solubilities. Entrapment or surface coating of chemotherapeutic agents in zein microneedles was optimized to achieve greater loading efficiency. Localized delivery of drugs decreases the adverse side effects [182]. Polymeric microneedles were tested against skin cancer and for localized anticancer drugs delivery. Ye et al. developed a melanin- mediated cancer immunotherapy strategy using a transdermal microneedle patch. B16F10 whole tumor lysate containing melanin is loaded into polymeric microneedles and allows sustained release of the lysate upon insertion of the microneedles into the skin. In combination with the near-infrared light irradiation, melanin produces local heat, which enhances the T cell activities by transdermal vaccines and encourages antitumor immune responses [183].

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