Octa-Arginine-Conjugated Liposomal Nimodipine Incorporated in a Temperature-Responsive Gel for Nasoencephalic Delivery.

Nimodipine is the primary clinical drug used to treat cerebral vasospasm following subarachnoid hemorrhage. Currently, tablets have low bioavailability when taken orally, and injections contain ethanol. Therefore, we investigated a new method of nimodipine administration, namely, nasoencephalic administration. Nasal administration of nimodipine was carried out by attaching the cell-penetrating peptide octa-arginine (R8) to liposomes of nimodipine and incorporating it into a temperature-sensitive in situ gel. The prepared liposomes and gels underwent separate evaluations for in vitro characterization. In vitro release exhibited a significant slow-release effect. In vitro toad maxillary cilia model, RPMI 2650 cytotoxicity, and in vivo SD rat pathological histotoxicity experiments showed that all the dosage from the groups had no significant toxicity to toad maxillary cilia, RPMI 2650 cells, and SD rat tissues and organs, and the cilia continued to oscillate up to 694 ± 10.15 min, with the survival rate of the cells being above 85%. A transwell nasal mucosa cell model and an isolated porcine nasal mucosa model were established, and the results showed that the osmolality of the R8-modified nimodipine liposomal gel to nasal mucosal cells and isolated porcine nasal mucosa was 30.41 ± 2.14 and 65.9 ± 7.34 µg/mL, respectively, which was significantly higher than that of the NM-Solution and PEGylated nimodipine liposome gel groups. Animal fluorescence imaging studies revealed that the R8-modified nimodipine liposomal gel displayed increased brain fluorescence intensity compared to the normal liposomal gel. Pharmacokinetic results showed that after transnasal administration, the AUC(0-∞) of the R8-modified nimodipine liposomal gel was 11.662 ± 1.97 µg·mL-1, which was significantly higher than that of the plain nimodipine liposomal gel (5.499 ± 2.89 µg·mL-1). Brain-targeting experiments showed that the brain-targeting efficiencies of the PEGylated nimodipine liposome gel and R8-modified PEGylated nimodipine liposome gels were 20.44 and 33.45, respectively, suggesting that R8/PEG/Lip-NM-TSG significantly increased the brain-targeting of the drug.

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6-Methylpyridine Moiety.

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (15a-t and 16a-f) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1-2 µg/mL) and 16d (MIC=0.5 µg/mL) showed the strongest antibacterial activities. Notably, compound 16d did not exhibit cytotoxicity in HepG2 cells and did not show hemolysis like the positive control compound Gatifloxacin. The results suggest that compound 16d should be further investigated as a candidate antibacterial agent.

Melatonin Induces Autophagy via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress Pathway in Colorectal Cancer Cells.

Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5'-adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.

Synthesis and biological evaluation of novel benzo[c][1,2,5]thiadiazol-5-yl and thieno[3,2-c]- pyridin-2-yl imidazole derivatives as ALK5 inhibitors.

Transforming growth factor (TGF-ß), a key mediator of tumor growth and metastasis, has been recognized as an important cancer drug target. A series of benzo[c][1,2,5]thiadiazol-5-yl imidazoles (14a-g) and thieno[3,2-c]-pyridin-2-yl imidazoles (20a-g) were designed, synthesized, and evaluated for their activin receptor-like kinase 5 (ALK5) activities. Among these compounds, 14c showed the highest activity (IC50 = 0.008 µM) against ALK5 kinase, which was 16.1-fold and 1.8-fold higher than those of positive control compounds LY-2157299 (IC50 = 0.129 µM) and EW-7197 (IC50 = 0.014 µM), respectively. Compound 14g (350) showed the highest selectivity index of ALK5 against p38α MAP kinase, which was significantly higher than that of positive control compounds LY-2157299 (4) and EW-7197 (211). The inhibitory effects of compound 14c on TGF-ß-induced Smad signaling and cell motility were studied in SPC-A1, HepG2 and HUVEC cells using western blot analysis and wound healing assay. ADMET prediction analysis showed that compounds 14c and 14g had good pharmacokinetics and drug-likeness behaviors.

Anodic composite deposition of RuO2/reduced graphene oxide/carbon nanotube for advanced supercapacitors.

Anodic composite deposition is demonstrated to be a unique method for fabricating a ternary ruthenium dioxide/reduced graphene oxide/carbon nanotube (RuO2 xH2O/rGO/CNT, denoted as RGC) nanocomposite onto Ti as an advanced electrode material for supercapacitors. The rGO/CNT composite in RGCs acts as a conductive backbone to facilitate the electron transport between current collector and RuO2 xH2O nanoparticles (NPs), revealed by the high total specific capacitance (C(S,T) = 808 F g(-1)) of RGC without annealing. The contact resistance among RuO2 xH2O NPs is improved by low-temperature annealing at 150 °C (RGC-150), which renders slight sintering and enhances the specific capacitance of RuO2 xH2O to achieve 1200 F g(-1). The desirable nanocomposite microstructure of RGC-150 builds up the smooth pathways of both protons and electrons to access the active oxy-ruthenium species. This nanocomposite exhibits an extremely high C(S,T) of 973 F g(-1) at 25 mV s(-1) (much higher than 435 F g(-1) of an annealed RuO2 xH2O deposit) and good capacitance retention (60.5% with scan rate varying from 5 to 500 mV s(-1)), revealing an advanced electrode material for high-performance supercapacitors.

[Treatment of Chronic Heart Failure with Carotid Plaque Patients by Yiqi Huoxue Tongyang Xezhuo Recipe].

OBJECTIVE: To evaluate the clinical effectiveness of Yiqi Huoxue Tongyang Xiezhuo Recipe (YHTXR, capable of supplementing qi, activating blood, warming yang, and discharge turbidity) in treating coronary atherosclerotic heart disease (CAHD). and chronic heart failure (CHF) with carotid plaque patients, and to explore new ways of Chinese medicine (CM). METHODS: Totally 69 CAHD-CHF patients of qi deficiency phlegm stasis syndrome (QDPSS) with carotid plaque were recruited in this study using parallel cohort method. They were assigned to the treatment group (35 cases) and the control group (34 cases). Patients in the control group received routine treatment of Western medicine, while those in the treatment group were additionally treated with YHTXR (twice daily). The therapeutic course for all was three months. Cardiac function levels, echocardiography, carotid plaque, blood lipids and safety indicators were observed before and after treatment. RESULTS: After treatment the improvement of cardiac function levels was better in the treatment group than in the control group (P < 0.05). Decreased LDL-C levels were higher in the treatment group than in the control group (P < 0.01). There was statistical difference in left ventricular ejection fraction (LVEF), carotid intima-media thickness (IMT), LDL-C, TC, TG in the treatment group between before and after treatment (P < 0.05). LDL-C and TG also decreased in the control group after treatment (P <0.05). There was no significant difference in the left ventricular ejection fraction, carotid IMT, or TC in the control group between before and after treatment (P > 0.05). There was no significant difference in stroke volume, left ventricular end-diastolic diameter, the area of carotid artery plaque, or HDL-C in the two groups between before and after treatment (P > 0.05). CONCLUSIONS: YHTXR could effectively improve cardiac functions of CAHD-CHF patients of QDPSS with carotid plaque, reduce blood lipids and IMT. It had no significant adverse reactions for elderly patients in short term.

Cancer Antibody Engineering: Comparison of Mammalian, Yeast, Bacterial, Plants, Cell-free and Hybridoma Expression Systems.

BACKGROUND: Cancer is a significant issue worldwide. Generally, commercially available treatments, such as surgery, radiotherapy, and chemotherapy, are associated with undesirable complications. Hence, immunotherapy serves as a crucial alternative to those treatment options. OBJECTIVE: This modality is aimed to boost the immune system through the application of engineered antibodies, which can be produced using recombinant DNA technology. RESULTS: The discussion of the technologies leads to an introduction of the single-chain variable fragment (scFv). Thereafter, the advantages, disadvantages, and challenges associated with different expression systems, such as mammalian cells, yeast cells, bacterial cells, plant cells, and phage display were discussed comprehensively. CONCLUSION: Furthermore, conventional approaches such as hybridoma and modern approaches such as cell-free protein synthesis (CFPS) and simple colony assays are included. In short, this article has compiled evidence relating to each display system and may serve as a reference for those who aim to explore antibody engineering using one of the methods listed in this article.

pH-Responsive and Mucoadhesive Nanoparticles for Enhanced Oral Insulin Delivery: The Effect of Hyaluronic Acid with Different Molecular Weights.

Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA-PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA-PDM-INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA-PDM-INS, M-HA-PDM-INS, H-HA-PDM-INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA-PDM-INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA-PDM-INS was investigated. The release of INS from H-HA-PDM-INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA-PDM-INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA-PDM-INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA-PDM-INS, regardless of the MW of HA, was demonstrated using CCK-8 and live-dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA-PDM-INS, M-HA-PDM-INS, and H-HA-PDM-INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA-PDM-INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.

Prevention of Parkinson's disease: from risk factors to early interventions.

Parkinson's disease (PD) is a debilitating neurological disorder characterized by progressively worsening motor dysfunction. Currently, available therapies merely alleviate symptoms, and there are no cures. Consequently, some researchers have now shifted their attention to identifying the modifiable risk factors of PD, with the intention of possibly implementing early interventions to prevent the development of PD. Four primary risk factors for PD are discussed including environmental factors (pesticides and heavy metals), lifestyle (physical activity and dietary intake), drug abuse, and individual comorbidities. Additionally, clinical biomarkers, neuroimaging, biochemical biomarkers, and genetic biomarkers could also help to detect prodromal PD. This review compiled available evidence that illustrates the relationship between modifiable risk factors, biomarkers, and PD. In summary, we raise the distinct possibility of preventing PD via early interventions of the modifiable risk factors and early diagnosis.

Preparation of Betulinic Acid Galactosylated Chitosan Nanoparticles and Their Effect on Liver Fibrosis.

Aim: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver. Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro. Results: BA-GC-NPs with diameters <200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GC-NPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BA-GC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice. Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.

Vitamin A - modified Betulin polymer micelles with hepatic targeting capability for hepatic fibrosis protection.

Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(VA) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of VA modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VAPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VAPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VAPPMs exhibited steady and continuous release for over 168 hours. Bt/VAPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VAPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VAPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VAPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.

Development of a clinical prediction rule to identify patients with neck pain who are likely to benefit from home-based mechanical cervical traction.

The objective of the study was to identify the population of patients with neck pain who improved with home-based mechanical cervical traction (HMCT). A prospective cohort study was conducted in a physical therapy clinic at a local hospital. Patients with neck pain referred to the clinic for physical therapy were included in the study. A HMCT program was given to participants for 2 weeks. The patient's demographic data, Numerical Pain Scale (NPS) score, Neck Disability Index (NDI) and Fear-Avoidance Beliefs Questionnaire score were collected, and standard physical examination of the cervical spine was conducted before intervention. The NPS score, NDI and a global rating of perceived improvement were collected after the intervention was completed. A total of 103 patients participated in the study and 47 had a positive response to HMCT. A clinical prediction rule with four variables (Fear-Avoidance Beliefs Work Subscale score < 13, pre-intervention pain intensity ≥ 7/10, positive cervical distraction test and pain below shoulder) was identified. With satisfaction of at least three out of four variables (positive likelihood ratio = 4.77), the intervention's success rate increased from 45.6% to over 80%. It appears that patients with neck pain who are likely to respond to HMCT may be identified.

Potential role of melatonin in prevention and treatment of leukaemia.

Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.

Edible Bird's Nest: Recent Updates and Industry Insights Based On Laboratory Findings.

Edible bird's nest (EBN) is a traditional Chinese delicacy made of the saliva of swiftlets found in Southeast Asia. With increasing demands for EBN, quality control of EBN products is important for safe consumption. The processing steps are particularly important for efficient extraction of bioactive compounds. Geographical location, collection place, and harvesting season contribute to differences in nutritional contents in EBN. Concerns regarding presence of adulterant, chemical, and microbial contaminants in EBN as well as authentication and chemical composition measuring methods are discussed in this review. Recent discoveries of beneficial health functions of EBN in antimicrobial and antiviral actions, immunomodulation, cancer prevention and treatment, tissue regeneration, cardiometabolic maintenance, antioxidant action and neuroprotection are also reviewed. Our review provides an update on the recent research on EBN.

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability.

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.

Enhanced bioavailability of poorly water-soluble clotrimazole by inclusion with beta-cyclodextrin.

Clotrimazole, a poorly water-soluble antimycotic agent, is a promising agent for various diseases including cancer and sickle cell anemia. To improve the oral bioavailability of clotrimazole, the inclusion compound of clotrimazole with beta-cyclodextrin was prepared by spray-drying method and characterized by phase solubility, differential scanning calorimetry and dissolution. Furthermore, the pharmacokinetics after oral administration in rats was then performed compared with clotrimazole powder. The solubility of clotrimazole increased linearly as a function of beta-cyclodextrin concentration, resulting in A(L) type phase solubility diagram which revealed a formation of inclusion compound in a molar ratio of 1:2, with the apparent association constant of 230.2 M(-1). The dissolution rate of clotrimazole in the inclusion compound increased greatly compared to clotrimazole powder in pH 7.4 phosphate buffer solution. The inclusion compound gave significantly higher initial plasma concentrations, Cmax and AUC of clotrimazole than did clotrimazole powder when they were administered as suspension form, indicating that the drug from inclusion compound could be more orally absorbed in rats. Thus, the oral bioavailability of clotrimazole could be improved markedly by inclusion complexation, possibly due to an increased dissolution rate.

Real-time quantitative reverse transcription-PCR assay for renal cell carcinoma-associated antigen G250.

OBJECTIVES: Gene amplification/expression of G250 is a major event in human renal tumorigenesis. G250-based therapeutic agents and G250-specific gene therapy are under development. These new perspectives call for a sensitive and accurate method to screen G250 alterations in renal cell cancer (RCC) patients and investigate the relationship between G250 mRNA expression and RCC. METHODS: We developed a quantitative RT-PCR assay for the measurement of G250 mRNA expression using a real-time procedure based on the use of fluorogenic probes and the ABI PRISM 7700 Sequence Detector System. The method has been applied to the measurement of quantitative mRNA level of G250 in 31 cases RCC and 6 normal renal tissues. RESULTS: The dynamic range was 10(3)-10(8). The relationship between Ct and log starting concentration was linear (r=0.99). G250 expression was present in all RCCs with G250 amplification but was absent in normal ones. G250 mRNA expression ranged from 2.9 x 10(3) to 6.5 x 10(7) copy/microg RNA, with a mean value of 3.5 x 10(6) copy/microg RNA. The expression of G250 revealed an inverse correlation to tumor grade. G250 mRNA level did not correlate with the cell types and clinical stages (P>0.05). CONCLUSIONS: G250 has the potential to be used as a marker of diagnosis and increasing proliferation in RCC. This new simple, rapid, semi-automated assay was a major alternative to competitive PCR and Northern blot analysis for gene alteration analysis in human tumors and might be a powerful tool for large randomized, prospective cooperative group trials and supporting future G250-based biological and gene therapy approaches.

Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent.

Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.

Effect of sodium carboxymethylcellulose and fucidic acid on the gel characterization of polyvinylalcohol-based wound dressing.

The purpose of this study was to investigate the effect of sodium carboxymethylcellulose (Na-CMC) and fucidic acid on the gel characterization for the development of sodium fucidate-loaded wound dressing. The cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method. Their gel properties such as gel fraction, swelling, water vapor transmission test, morphology, tensile strength and thermal property were investigated. In vitro protein adsorption test and release were performed. Na-CMC decreased the gel fraction and tensile strength of the hydrogels, but increased the swelling ability, water vapor transmission rate, elasticity and porosity of hydrogels. Thus, the wound dressing developed with PVA and Na-CMC was more swellable, flexible and elastic than that with only PVA because of its cross-linking interaction with PVA. However, the drug had a negative effect on the gel properties of hydrogels but there were no significant differences. In particular, the hydrogel composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug might give an adequate level of moisture and build up the exudates on the wound area. Thus, this sodium fucidate-loaded hydrogel could be a potential candidate for wound dressing with excellent forming.

Preparation and in vivo evaluation of piroxicam-loaded gelatin microcapsule by spray drying technique.

To develop a piroxicam-loaded gelatin microcapsule with enhanced bioavailability, a gelatin microcapsule encapsulated ethanol and piroxicam has been formulated by using gelatin as a water-soluble polymer shell. The aqueous solubility and bioavailability of piroxicam in piroxicam-loaded microcapsule in rats were then evaluated compared to piroxicam powder. The piroxicam-loaded gelatin microcapsule spherical in shape with smooth surface showed the geometric mean diameter of about 19 microm. It had the piroxicam solubility of about 1.87 mg/ml and the amount of ethanol of about 4.37 microg/mg. Furthermore, it gave significantly higher total plasma concentrations, Cmax and area under the blood concentration-time curve (AUC) of piroxicam in rats than did piroxicam powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. In particular, the AUC of piroxicam in gelatin microcapsule was significantly about 2 fold increased compared to piroxicam powder. This enhanced oral relative bioavailability of piroxicam in gelatin microcapsule was contributed by the marked increase in the absorption rate of piroxicam due to the improved solubility of piroxicam. Thus, the piroxicam-loaded gelatin microcapsule developed using spray-drying technique with gelatin, sodium lauryl sulfate and ethanol would be useful to deliver piroxicam in a pattern that allows fast absorption in the initial phase, leading to better absorption.