Ultrasound-guided median nerve electrical stimulation to promote upper limb function recovery after stroke

Peripheral electrical nerve stimulation enhances hand function during stroke rehabilitation. Here, we proposed a percutaneous direct median nerve stimulation guided by ultrasound (ultrasound‐guided median nerve electrical stimulation, UG-MNES) and evaluated its feasibility and effectiveness in the treatment of stroke patients with upper limb extremity impairments. Sixty-three stroke patients (2-3 months of onset) were randomly divided into control and UG-MNES groups. Both groups received routine rehabilitation and the UG-MNES group received an additional ultrasound-guided electrical stimulation of the median nerve at 2 Hz, 0.2 ms pulse-width for 20 minutes with gradual intensity enhancement. The Fugl-Meyer Assessment for upper extremity motor function (FMA-UE) was used as the primary outcome. The secondary outcomes were the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK), Hand Function Rating Scale, Brunnstrom Stages, and Barthel Index scores for motor and daily functions. All the participants completed the trial without any side effects or adverse events during the intervention. After 4 weeks of intervention, the functions of the upper limbs on the hemiplegic side in both groups achieved significant recovery. Compared to the control group, all evaluation indices used in this trial were improved significantly in the UG-MNES group after 2 and 4 weeks of intervention; particularly, the first intervention of UG-MNES immediately improved all the assessment items significantly. In conclusion, the UG-MNES is a safe and feasible treatment for stroke patients with upper limb extremity impairments and could significantly improve the motor function of the affected upper limb, especially in the first intervention. The UG-MNES could be an effective alternative intervention for stroke with upper limb extremity impairments

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

Background: Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods: To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion-solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%+/- 0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%+/- 1.01% and BH loaded into Eudragit microspheres was 14.31%+/- 0.47%. Results: Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion: The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma

Case report: Ultrasound-guided median nerve electrical stimulation on functional recovery of hemiplegic upper limb after stroke

Background: Functional restoration of hemiplegic upper limbs is a difficult area in the field of neurological rehabilitation. Electrical stimulation is one of the treatments that has shown promising advancements and functional improvements. Most of the electrical stimulations used in clinical practice are surface stimulations. In this case, we aimed to investigate the feasibility of a minimally invasive, ultrasoundguided median nerve electrical stimulation (UG-MNES) in improving the upper limb motor function and activity of a patient with right-sided hemiparesis. Case presentation: A 65-year-old male recovering from a left massive intracerebral hemorrhage after open debridement hematoma removal had impaired right limb movement, right hemianesthesia, motor aphasia, dysphagia, and complete dependence on his daily living ability. After receiving 3  months of conventional rehabilitation therapy, his cognitive, speech, and swallowing significantly improved but the Brunnstrom Motor Staging (BMS) of his right upper limb and hand was at stage I-I. UG-MNES was applied on the right upper limb for four sessions, once per week, together with conventional rehabilitation. Immediate improvement in the upper limb function was observed after the first treatment. To determine the effect of UG-MNES on long-term functional recovery, assessments were conducted a week after the second and fourth intervention sessions, and motor function recovery was observed after 4-week of rehabilitation. After completing the full rehabilitation course, his BMS was at stage V-IV, the completion time of Jebsen Hand Function Test (JHFT) was shortened, and the scores of FuglMeyer Assessment for upper extremity (FMA-UE) and Modified Barthel Index (MBI) were increased. Overall, the motor function of the hemiplegic upper limb had significantly improved, and the right hand was the utility hand. Electromyography (EMG) and nerve conduction velocity (NCV) tests were normal before and after treatment. Conclusion: The minimally invasive, UG-MNES could be a new alternative treatment in stroke rehabilitation for functional recovery of the upper limbs

Incorporation of ion exchange functionalized-montmorillonite into solid lipid nanoparticles with low irritation enhances drug bioavailability for glaucoma treatment

Montmorillonite-loaded solid lipid nanoparticles with good biocompatibility, using Betaxolol hydrochloride as model drug, were prepared by the melt-emulsion sonication and low temperature-solidification methods and drug bioavailability was significantly improved in this paper for the first time to application to the eye. The appropriate physical characteristics were showed, such as the mean particle size, Zeta potential, osmotic pressure, pH values, entrapping efficiency (EE%) and drug content (DC%), all showed well suited for possible ocular application. In vitro release experiment indicated that this novel system could continuously release 57.83% drugs within 12 h owing to the dual drug controlled-release effect that was achieved by ion-exchange feature of montmorillonite and structure of solid lipid nanoparticles. Low irritability and good compatibility of nanoparticles were proved by both CAM-TBS test and cytotoxicity experiment. We first discovered from the results of Rose Bengal experiment that the hydrophilicity of the drug-loaded nanoparticles surface was increased during the loading and releasing of the hydrophilic drug, which could contribute to prolong the ocular surface retention time of drug in the biological interface membrane of tear-film/cornea. The results of in vivo pharmacokinetic and pharmacodynamics studies further confirmed that increased hydrophilicity of nanoparticles surface help to improve the bioavailability of the drug and reduce intraocular pressure during administration. The results suggested this novel drug delivery system could be potentially used as an in situ drug controlled-release system for ophthalmic delivery to enhance the bioavailability and efficacy

Dual controlled release effect of montmorillonite loaded polymer nanoparticles for ophthalmic drug delivery

Montmorillonite based polymeric nanoparticles was designed to effectively deliver adequate concentrations of drug to the ocular site after topical administration for treatment of glaucoma. In vitro and in vivo studies were carried out to evaluate their drug delivery performances. Betaxolol hydrochloride (BH) intercalated montmorillonite (Mt-BH) was successfully encapsulated into the Eudragit (R) PO (Mt-BH NPs) via an opportunely emulsification-solvent evaporation technique as indicated by Fourier transform infrared, differential scanning calorimentry, and the nitrogen sorption and desorption isotherms. The resulting nanoparticle system showed the mean particle diameters of 82 +/- 8 nm and positive. potentials, with encapsulation efficiency of 77 +/- 1% and drug-loading rate of 8 +/- 2%. Interestingly, in vitro release profile of Mt-BH NPs exhibits an initial burst of surface-bound BH, followed by a slow release of BH due to polymer erosion, and a further drug release after the particle completely breakdown. About 80% were released after 10 h. The designed drug delivery system showed little irritation and well tolerance of nanoparticles in a chorioallantoic membrane assay. The new Eudragit (R) PO polymer nanoparticles system reported here is expected to be useful in ophthalmic application