Microneedles of chitosan‐porous carbon nanocomposites: Stimuli (pH and electric field)‐initiated drug delivery and toxicological studies

Abstract

An array of microneedles (MNs) of chitosan‐graphene assembled in porous carbon (CS‐GAPC) nanocomposites has been synthesized and evaluated. The safety of the formulated system has been ensured using detailed in vivo toxicological studies and efficacy has been ensured by evaluating the stimuli (pH and electric field) initiated drug delivery properties. Drug cephalexin has been incorporated in these MNs. In vivo toxicological studies of CS‐GAPC nanocomposite were performed on Sprague rats, using acute dermal and subacute dermal (ADT& SADT) test, histopathological studies, biochemical studies, and AMES tests. ADT and SADT studies showed that median lethal dose (LD50) was found greater than 2000 mg/kg body weight; with no abnormal weight gain and food consumption, during the study period of 28 days. This study showed that administration of CS‐GAPC did not cause any substantial alterations in hematological and biochemical parameters of the animals. Histopathological studies showed no significant changes in the control and CS‐GAPC administered groups. AMES tests reveal that CS‐GAPC nanocomposite is nonmutagenic against the Salmonella thyphimurium strains. No abnormalities were observed in the animal's chromosomal aberrations and clastogenic values when the animals were treated with CS‐GAPC. At acidic pH of 4, the encapsulated drug was completely released, indicating that the drug release from the prepared nanocomposite is pH dependent. An electric field of 5 V showed optimum drug release, as a function of applied electric pulses. A biologically safe drug encapsulation model system is hence projected for smart drug delivery (pH dependent and electric field triggered) using the microneedle approach. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1582–1596, 2019.

Smart microneedle patches for wound healing and management

“…Precise regulation of the time, area, and flow rate of drug release can effectively improve the wound environment. 100 Signals that can be responsive include physical and chemical signals, such as light, 101–104 electricity, 105 magnetism, 106 temperature, 87,107,108 pH, 109 glucose, 110 and ROS. 111…”

“…Precise regulation of the time, area, and flow rate of drug release can effectively improve the wound environment. 100 Signals that can be responsive include physical and chemical signals, such as light, [101][102][103][104] electricity, 105 magnetism, 106 temperature, 87,107,108 pH, 109 glucose, 110 and ROS. 111 Near infrared (NIR) light has received attention due to its ease of manipulation, ability to locally focus on a specific site, and its safety, allowing non-invasive propagation in deeper tissues.…”

Stimuli-Responsive Microneedles as a Transdermal Drug Delivery System: A Demand-Supply Strategy

“…In such conditions, the dual stimuli-responsive MNs are capable of treating superficial tumors under one stimulus and managing the encountered pain under another stimulus. In support of this statement, a recent study by Gaware and team developed both pH and electric-current-responsive single MN patch for on-demand transdermal drug delivery, 173 where pH was utilized to trigger the drug release only at the site of superficial tumors and electric current was considered to spatiotemporally control the drug release for pain management.…”

Microneedle-Mediated Transdermal Delivery of Drug-Carrying Nanoparticles

“…However, the use of iontophoresis alone still has limited improvement and do not significantly promote drug penetration from stratum corneum to deeper layers (e.g., Epidermis and dermis), especially for those biological macromolecules such as proteins or DNA. The strategy of combining iontophoresis with MNs can significantly improve the transdermal delivery efficiency as well as broaden the diversity of drugs ranging from small chemicals to large molecules or drugloaded nanoparticles (Katikaneni et al, 2009;Lanke et al, 2009;Vemulapalli et al, 2012;Gaware et al, 2019). For example, Chen et al investigated the transdermal delivery of insulin-loaded nanovesicles driven by iontophoresis through microchannels created by solid MNs (Chen et al, 2009).…”