Preparation Of RbFGF/CPC-Loaded Dissolvable Microneedles Patch And Its Therapeutic Effect On RAU

Objective: Conventional topical medications for RAU are limited due to the washing effect of saliva decreasing the local effective drug concentration,short duration of action and the surface barrier of pseudomembranous.To overcome this drawback,sodium hyaluronate(HA)microneedles(MNs)patch loading recombinant bovine basic fibroblast growth factor(rb FGF)and cetylpyridinium chloride(CPC)was prepared and examined for the therapeutic effect on rat animal model of RAU.Methods: The rb FGF/CPC loaded-MNs were prepared via two-casting method and the drug was released when the soluble polymer matrix HA rapidly dissolving.The morphology,structure and mechanical properties of MNs were characterized by stereomicroscope,SEM and universal testing machine.The MNs were inserted into the oral mucosa of rats and soaked in artificial saliva to determine the dissolution rate of the needle tip and substrate.The antibacterial test was performed using the plate count method and subsequently the toxicity of the composite against L929 mouse fibroblast was measured by MTT and LIVE/DEAD staining methods.Animal models of RAU were constructed in gingival mucosal area on maxillary central incisor of SD rats utilizing 50% glacial acetic acid by chemical induction.The animals were divided into control group,HA microneedle group,CPC HA microneedle group,rb FGF HA microneedle group,rb FGF/CPC HA microneedle group and the conventional treatment group.After modeling,the drug was administered once a day for each group until 7days later when the final treatment results were observed.Finally,rats were sacrificed and ulcer samples were collected and sectioned for histochemical and immunofluorescence staining to evaluate the healing efficacy.Results:(1)Morphological measurement revealed that orderly arranged 121(11×11)MNs with highly homogenous and conical shape on each patch and MNs was consists of approximately 564.23 ± 6.97 μm height,281.55 ± 5.16 μm base diameter and 576.31 ±10.06 μm interval.The model drug was mainly dispersed in the tips of MNs with good dispersity under fluorescence microscope.The HA MNs showed highly porous structure and mechanical property as 77.82 ± 1.22 KPa compressive strength.Meanwhile,MNs were dissolved about 76.95 ± 1.61% of their initial height after insertion of oral mucosa and 86.5 ± 2.34% of their initial weight after soaked into artificial saliva for 5 mins.(2)The rb FGF/CPC loaded-MNs presented favorable antibacterial properties against E.coli,S.aureus and S.mutans,the inhibition ratio of these three bacteria enhanced with the increase of sample concentration.MTT and LIVE/DEAD staining results showed that the rb FGF/CPC loaded-MNs should be biocompatible with no obvious cytotoxicity against L929 mouse fibroblast.(3)7 days after RAU model rats were treated with different groups,the rb FGF/CPC HA microneedle group significantly increased the proliferation of oral epithelial cells and obviously promoted the ulcer healing.Conclusions:To sum up,MNs patches for RAS as a modified administration was successfully fabricated through a simple and moderate method.CPC and rb FGF were loaded into HA matrix by physical mixing and the production process being divided into two steps ensured that the drug was gathered at the tip of the needles.It could overcome the disadvantages of the current administration and achieve better ulcer healing.Thus,b FGF/CPC-loaded MNs have a potential to be applied in oral ulcers as a novel treatment.MNs patch presents high delivery capacity and conveniences,as a drug delivery platform for broad application.