Microneedle array patches for sustained delivery of fluphenazine: A micron scale approach for the management of schizophrenia.

Schizophrenia is a severe chronic mental illness characterised by impaired emotional and cognitive functioning. To treat this condition, antipsychotics are available in limited dosage forms, mainly oral and injectable formulations. Although injectable antipsychotics were designed to enhance adherence, they are invasive, painful and require a healthcare professional to be administered. To overcome such administration issues, extensive research has been focused on developing transdermal antipsychotic formulations. In this work, three microneedle (MN) systems were developed to deliver fluphenazine (FLU) systemically. A decanoic prodrug of FLU called fluphenazine decanoate (FLUD) was used in two of the MN formulations due to its high lipophilicity. FLU-D was loaded into dissolving MNs and nanoemulsion (NE)-loaded MNs. The parent drug FLU was loaded into poly(lactic-co-glycolic acid) (PLGA)-tipped MNs. All MN systems were characterised and evaluated in vitro and in vivo. The in vivo evaluation of the three developed MN systems showed their ability to deliver FLU into the systemic circulation, as the Cmax of FLU-D dissolving MNs was 36.11 ± 12.37 ng/ml. However, the Cmax of FLU-D NE loaded dissolving MNs was 12.92 ± 6.3 ng/ml and for FLU-PLGA tipped MNs was 21.57 ± 2.45 ng/ml. Compared to an intramuscular (IM) injection of FLU-D in sesame oil, the relative bioavailabilities were 26.96 %, 21.73 % and 42.45 % for FLU-D dissolving MNs, FLU-D NE dissolving MNs and FLU-PLGA tipped MNs, respectively. FLU plasma levels were maintained above the minimum human therapeutic limits for a week. Consequently, these various MN formulations are considered to be a viable options for the transdermal delivery of fluphenazine and its prodrug. The three MN systems developed offer patients a user-friendly, painless, and convenient long-acting delivery method for FLU. Reducing dosing frequency and using less invasive drug administration methods can enhance adherence and foster positive therapeutic outcomes. This study demonstrates the capability and adaptability of MNs technology to transport hydrophobic molecules from the skin to the systemic circulation.

Smart Responsive Microarray Patches for Transdermal Drug Delivery and Biological Monitoring.

Traditional drug delivery routes possess various disadvantages which make them unsuitable for certain population groups, or indeed unsuitable for drugs with certain physicochemical properties. As a result, a variety of alternative drug delivery routes have been explored in recent decades, including transdermal drug delivery. One of the most promising novel transdermal drug delivery technologies is a microarray patch (MAP), which can bypass the outermost skin barrier and deliver drugs directly into the viable epidermis and dermis. Unlike traditional MAPs which release loaded cargo simultaneously upon insertion into the skin, stimuli responsive MAPs based on biological stimuli are able to precisely release the drug in response to the need for additional doses. Thus, smart MAPs that are only responsive to certain external stimuli are highly desirable, as they provide safer and more efficient drug delivery. In addition to drug delivery, they can also be used for biological monitoring, which further expands their applications.