Multiple sclerosis (MS) is a chronic neurological disease where immune cells from the periphery enter the central nervous system and attack the myelin sheaths resulting in damage to the axons. It is an unpredictable disease that affects each person differently. One of the symptoms of MS includes muscle spasticity and depending on the severity it can cause gait and mobility issues. Oral baclofen is the first-line recommendation to treat spasticity in people with MS whose treatment goals include improving mobility or easing pain and discomfort. Baclofen works pre- and post-synaptically as a gamma aminobutyric acid-B agonist at the spinal cord to reduce the amount of excitatory neurotransmitters that are responsible for muscle contractions. Oral baclofen has been used to treat spasticity, however its short half-life of 2-6 hours warrants its need for three times a day dosing schedule. The multiple daily dosing can be a burden to the patient taking it and for the caregiver who will be giving the medication which can negatively affect adherence and acceptability. The goal of the current study was to design and assess baclofen loaded dissolving microneedle (MN) patch on the amount permeated and sustained delivery of baclofen in the management of spasticity. A 1.5 mg/mL MN patch was initially made by dissolving baclofen in polyvinylpyrrolidone (PVP) and fabricated using the mold casting technique. The permeation profile of fabricated baclofen loaded MNs over a predetermined time was assessed in vitro through dermatomed porcine ear skin using Franz Diffusion cells. Employing the use of MNs significantly increased the flux from 2.10 ± 0.35 µg/sq.cm/h to 5.92 ± 4.17 µg/sq.cm/h and the average cumulative amount permeated from 92.67 ± 11.25 µg/sq.cm to 457.11 ± 111.47 µg/sq.cm over 72 h (p<0.05). However, because of baclofen’s hydrophilic nature, drug permeation across skin is limited, so a nanosuspension with reduced particle size was formulated to be used for MN fabrication to increase drug loading and permeation. Baclofen was formulated into a suspension through wet media milling followed by mechanical homogenization using PVP K30 and sodium dodecyl sulfate as stabilizers. The suspension was successfully loaded in dissolving PVP-based MNs. The donor chamber of the cell contained the MN patch mounted onto the porcine skin and the receptor chamber contained phosphate buffered saline. The receptor was sampled over 72 h and analyzed using HPLC. The baclofen suspension loaded MNs produced an average drug flux of 26.51 ± 4.17 µg/sq.cm/h and an average cumulative amount of 1718.96 ± 217.12 µg/sq.cm over 72 h. The use of suspension loaded MNs was found to enhance the permeation and produce a sustained delivery of baclofen across skin and depicts the applicability of fabricated needles for sustained delivery in the management of muscle spasticity in multiple sclerosis.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:asrf-2111 |
| Date | 25 April 2023 |
| Creators | Verana, Gabrielle, Tijani, Akeemat Oluwafisayo, Lessaint, Rebecca, Al Shawi, Maryan, Mahida, Krishna, Puri, Ashana |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | Appalachian Student Research Forum |
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