Novel Double-Layer Dissolving Microneedles for Transmucosal Sequential Delivery of Multiple Drugs in the Treatment of Oral Mucosa Diseases.

The development of transmucosal drug delivery systems is a practical requirement in oral clinical practice, and controlled sequential delivery of multiple drugs is usually required. On the basis of the previous successful construction of monolayer microneedles (MNs) for transmucosal drug delivery, we designed transmucosal double-layer sequential dissolving MNs using hyaluronic acid methacryloyl (HAMA), hyaluronic acid (HA), and polyvinyl pyrrolidone (PVP). MNs have the advantages of small size, easy operation, good strength, rapid dissolution, and one-time delivery of two drugs. Morphological test results showed that the HAMA-HA-PVP MNs were small and intact in structure. The mechanical strength and mucosal insertion test results indicated the HAMA-HA-PVP MNs had appropriate strength and could penetrate the mucosal cuticle quickly to achieve transmucosal drug delivery. The in vitro and in vivo experiment results of the double-layer fluorescent dyes simulating drug release revealed that MNs had good solubility and achieved stratified release of the model drugs. The results of the in vivo and in vitro biosafety tests also indicated that the HAMA-HA-PVP MNs were biosafe materials. The therapeutic effect of drug-loaded HAMA-HA-PVP MNs in the rat oral mucosal ulcer model demonstrated that these novel HAMA-HA-PVP MNs quickly penetrated the mucosa, dissolved and effectively released the drug, and achieved sequential drug delivery. Compared to monolayer MNs, these HAMA-HA-PVP MNs can be used as double-layer drug reservoirs for controlled release, effectively releasing the drug in the MN stratification by dissolution in the presence of moisture. The need for secondary or multiple injections can be avoided, thus improving patient compliance. This drug delivery system can serve as an efficient, multipermeable, mucosal, and needle-free alternative for biomedical applications.

Composite dissolvable microneedle patch for therapy of oral mucosal diseases.

A composite microneedle patch (MN patch) is developed for oral transmucosal administration. To improve the oral transmucosal drug delivery efficiency, the composite MN patch is designed to consist of an array of 100 dissolvable microneedles (MNs) with drug-loaded tips and a backing layer. The MNs are composed of two parts, the hyaluronic acid (HA) tip part and the polyvinylpyrrolidone (PVP) base part. Due to the small size and sufficient mechanical strength, the HA-PVP MNs can painlessly penetrate the oral mucosa barrier and deliver drugs directly to the basal layer or submucosa. Betamethasone sodium phosphate (BSP), as the model drug, is concentrated in the HA tip parts to avoid the drug waste caused by mucosa elasticity. Considering the special moist environment and saliva flow in the mouth, a double-layer backing layer composed of a poly(vinyl alcohol) (PVA) adhesive layer and an ethyl cellulose (EC) waterproof layer is designed and constructed, which could reduce the saliva flow effects. The in vitro and in vivo results demonstrate that the MN patch could achieve rapid and efficient BSP release in oral mucosa due to the rapid dissolution of HA. The proposed MN patch provides a novel strategy for the therapy of oral mucosal diseases.

Distribution of Diego blood group alleles and genotypes in the Chinese Korean population and sequence-based identification.

OBJECTIVE: To investigate Diego blood group alleles in the Chinese Korean population. The Diego blood group system plays an important role in transfusion medicine, but the distribution of the blood group in many Chinese ethnic populations remains unclear. METHODS: Sequence Specific Primer Polymerase Chain Reaction (SSP-PCR) was used for Diego genotyping and sequence-based typing PCR (PCR-SBT) was used to verify single nucleotide polymorphisms in the coding region of SLC4A1 starting from exon 19. Nine hundred and ten samples from the Chinese Korean population were investigated. RESULTS: The frequency of the DI*01 and DI*02 alleles in the Chinese Korean population was 0.0516 and 0.9484, respectively. The most predominant genotype was DI*02/DI*02, with a frequency of 90.22 % (821/910). The frequency of DI*01/DI*02 was 9.23 % (84/910) and that of DI*01 /DI*01 was 0.55 % (5/910). The genotype distributions of the Diego blood group conformed to the Hardy-Weinberg equilibrium (P > 0.05). CONCLUSION: The data obtained from this study will be helpful for the creation of a donor database to provide antigen-negative blood to patients with allo-antibodies. Genotyping can be used as a substitute for the serological technique when antisera are unavailable and is suitable for screening a large number of donors for rare-blood-group databases.

Polymorphism of KIR gene family in Korean ethnic group of Jilin area / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the polymorphism of natural killer cell immunoglobulin-like receptor (KIR)gene and the characteristics of its genotypes and haplotypes in Korean ethnic group of Jilin area, and to compare with that of Han nationality.</p><p><b>METHODS</b>DNA samples randomly collected from 214 Han and 160 Korean populations were genotyped with PCR-SSP method, and KIR genotypes and haplotypes were assigned according to the standard model by Hsu et al.</p><p><b>RESULTS</b>All individuals contain KIR 3DL3, KIR 2DL4, KIR 3DL2 with the genotype frequency of 100%; the most common genotypes were 2DL1, 2DL3, 3DL1, 3DP1(*)003 and 2DP1; the genotypes with low frequency were 2DL2, 2DS2, 2DS3, 3DP1(*)001/002/004. Thirty-nine different KIR genotype and 16 haplotypes had been found in Korean and Han individuals. The most common KIR genotypes were AJ and AF with frequency of 18.1%, 19.4% and 31.8%, 19.6%, respectively. The most common KIR haplotype was haplotype 2 with frequency of 41.8% (n = 127) and 51.2% (n = 216) (P < 0.05), respectively.</p><p><b>CONCLUSION</b>KIR gene distribution in Jilin Korean ethnic group showed some common features of KIR gene polymorphisms in Chinese Han population, but also showed this nation's unique characteristics of KIR gene polymorphism.</p>

[Influence of cervical curvature change on the nerve root and vertebral artery of patients with cervical spondylosis and clinical observation of manipulation treatment].

OBJECTIVE: To observe the influence of the change of cervical curvature on the nerve root and the vertebral artery of the patients with cervical spondylosis and the curative effect of therapeutic manipulations. METHODS: Sixty cases of cervical spondylosis with the change of cervical curvature, 60 cases of cervical spondylosis without the change of cervical curvature and 60 normal people were chosen. They were clinically observed and the cervical spondylosis was treated by manipulations and the data was processed according to the principle of statistics. RESULTS: The change of cervical curvature affected the nerve root and the vertebral artery and therapeutic manipulations produced a satisfactory curative effect. CONCLUSION: Cervical spondylosis with change of cervical curvature has special characteristics in the etiology, course and state of the disease. The change of cervical curvature produces an effect on the nerve root and the vertebral artery. Selected therapeutic manipulations produce a better curative effect.