Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation.

OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

Comparative Study on Volatile Oils among Bupleuri radix Species and Habitats: Yields, Chemical Characterization and Antipyretic Activities.

Volatile oils from several Bupleuri radix (BR) are reported as potential sources of drugs. To provide evidence for the application of BR, the volatile oils from 19 batches of different species and habitats of BR including Bupleurum chinese DC. (BCD), Bupleurum scorzonerifolium Willd. (BSW), Bupleurum bicaule Helm (BBH), Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y.Li (BMS), Bupleurum marginatum Wall.ex DC. (BMW) and Bupleurum falcatum L. (BFL) were investigated. The composition of BR volatile oils was determined by GC/MS. Samples were clustered by hierarchical cluster analysis (HCA). Fever was induced by Lipopolysaccharide (LPS), and antipyretic activities of BR volatile oils were evaluated with Chaihu injection (CI) as the positive control. The yields of volatile oils were among 360-5320 ppm. A total of 229 components were identified by GC/MS. Samples could be divided into 4 clusters by HCA. 4 representative samples, one for each cluster, were selected to further compare their antipyretic activities. For the highest content of volatile oil (5320 ppm) and the best activity, BSW has great potential for utilization.

Mafenide derivatives inhibit neuroinflammation in Alzheimer's disease by regulating pyroptosis.

The main mechanism of pyroptosis is Caspase-1-mediated GSDMD cleavage, and GSDMD is also the executive protein of pyroptosis. Our previous study has shown that mafenide can inhibit pyroptosis by inhibiting the GSDMD-Asp275 site to suppress cleavage. In this study, sulfonamide was used as the parent nucleus structure to synthesize sulfa-4 and sulfa-20. Screening of drug activity in the pyroptosis model of BV2 and iBMDM cell lines revealed the efficacy of five compounds were superior to mafenide, which exerted a better inhibitory effect on the occurrence of pyroptosis. For in vivo assay, Sulfa-4 and Sulfa-22 were intervened in the neuroinflammation APP/PS1 mice. As a result, the administration of Sulfa-4 and Sulfa-22 could significantly inhibit the activation of microglia, decrease the expression of inflammatory factors in the central nervous system and simultaneously suppress the production of p30-GSDMD as well as the expression of upstream NLRP3 inflammasome and Caspase-1 protein. Immunoprecipitation and Biotin-labelled assay confirmed the targeted binding relationship of Sulfa-4 and Sulfa-22 with GSDMD protein in the iBMDM model in vitro. In this study, we investigated a new type inhibitor of GSDMD cleavage, which exerted a good inhibitory effect on pyroptosis and provided new references for the development of inflammatory drugs in the future.

Clinical and Economic Evaluation of Ultrasound-Guided Radiofrequency Ablation vs. Parathyroidectomy for Patients with Primary Hyperparathyroidism: A Cohort Study.

RATIONALE AND OBJECTIVES: To compare the clinical and economic effects of ultrasound (US)-guided radiofrequency ablation (RFA) with parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: From April 2014 to April 2021, 123 PHPT patients who received US-guided RFA or PTX were studied. Propensity score (PS) matching was used to balance the baseline data of the two groups. The rates of cure, recurrent and persistent PHPT, and complications were compared. A Chinese healthcare system perspective cost minimization analysis was conducted. RESULTS: After PS matching, 37 patient pairs (1:1) were created for the two groups. Follow-up was 27.2 ± 10.6 months and 28.8 ± 16.1 months for the RFA and PTX groups, respectively. At the last follow-up, there was no evidence of differences regarding clinical cure rate between the two groups (RFA vs. PTX, 91.9% vs. 94.6%, p = 1.000). Recurrent PHPT did not develop in any patient. One patient in each group had persistent PHPT. The incidence of complications and side effects, except postoperative pain (RFA vs. PTX, 16.2% vs. 40.5%, p = 0.020), were no significant difference between the two groups (all, p > 0.05). The incremental cost was -$284.00; thus, RFA was more cost-effective. For patients with employee medical insurance or resident medical insurance, the incremental costs (RFA vs. PTX) were -$391.94 and -$49.43, respectively. CONCLUSION: There were no significant differences in efficacy and safety between RFA and PTX. As the incremental cost for RFA compared with PTX was negative, RFA may be used as a more cost-effective nonsurgical treatment alternative for PHPT.

Study of ultrasound-guided percutaneous microwave ablation combined with portal vein embolization for rapid future liver remnant increase of planned hepatectomy.

Purpose: To evaluate the efficacy of ultrasound-guided percutaneous microwave ablation (PMA) combined with portal vein embolization (PVE) for planned hepatectomy. Methods: We retrospectively reviewed data of 18 patients with multiple right liver tumors or hilar tumor of liver invades the surrounding tissue and insufficient future liver remnant (FLR) for hepatectomy from July 2015 to March 2017. Ultrasound-guided PMA was performed by using PMCT cold circulation microwave treatment apparatus. PVE was performed after PMA. The increase of FLR was evaluated by computed tomography (CT) 6-22 days after PVE. The proportion of FLR, increase in the amplitude of FLR, procedure-related complications, perioperative morbidity and mortality, and overall survival (OS) rates, the median survival time were analyzed. Results: The median volume of FLR before PMA and PVE was 369.7 ml (range: 239.4-493.1 ml). After a median waiting period of 11.5 days (range: 6-22 days), the median volume of FLR was increased to 523.4 ml (range: 355.4-833.3 ml). The changes in FLR before and after PMA and PVE were statistically significant (p<0.001). No serious perioperative complications or mortality were found. After a median follow-up time of 51.0 months (range: 2-54 months), the 6-month, 1-year, 2-year, 3-year and 4-year survival rates were 88.9%, 72.2%, 44.4%, 33.3%, 22.2%, respectively, and the median survival time was 15.0 ± 7.1 months. Conclusion: PMA combined with PVE increases FLR rapidly, avoids touching malignant tumors, and produces fewer procedure-related complications. It appears safe and efficacious for planned hepatectomy.

Vinegar-baked Radix Bupleuri enhances the liver-targeting effect of rhein on liver injury rats by regulating transporters.

OBJECTIVE: This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury. METHODS: The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays. KEY FINDING: VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein. CONCLUSION: VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.

Efficacy and Safety of Ultrasound-Guided Radiofrequency Ablation for Primary Hyperparathyroidism: A Prospective Study.

OBJECTIVE: To assess the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) in patients with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: This prospective study enrolled 39 participants (14 male, 25 female; mean age, 59.5 ± 15.3 [range, 18-87] years) between September 1, 2018, and January 31, 2021. All participants had parathyroid lesions causing PHPT, proven biochemically and through imaging. The imaging features of the PHPT nodules, including the shape, margin, size, composition, and location, were evaluated before treatment. Serum intact parathyroid hormone, calcium, and phosphorus levels; parathyroid nodule volume; and PHPT-related symptoms were recorded before and after treatment. We calculated the technical success, biochemical cure, and clinical cure rates for these patients. Complications were evaluated during and after the ablation. RESULTS: Complete ablation was achieved in 38 of the 39 nodules in the 39 enrolled participants. All the patients were treated in one session. The technical success rate was 97.4% (38/39). The mean follow-up duration was 13.2 ± 4.6 (range, 6.0-24.9) months. At 6 and 12 months post-RFA, the biochemical cure rates were 82.1% (32/39) and 84.4% (27/32), respectively, and the clinical cure rates were 100% (39/39) and 96.9% (31/32), respectively. Only 2.6% (1/39) of the patients had recurrent PHPT. At 1, 3, 6, and 12 months after technically successful RFA, 44.7% (17/38), 34.3% (12/35), 15.8% (6/38), and 12.5% (4/32) of participants, respectively, had elevated eucalcemic parathyroid hormone levels. Recurrent laryngeal nerve paralysis occurred in 5.1% (2/39) of the patients, who recovered spontaneously within 1-3 months. CONCLUSION: US-guided RFA was effective and safe for PHPT patients. RFA may be an alternative treatment tool for patients who cannot tolerate or refuse to undergo surgery.

Prediction model that combines with multidisciplinary analysis for clinical evaluation of malignancy risk of solid breast nodules.

OBJECTIVE: Few studies have systematically developed predictive models for clinical evaluation of the malignancy risk of solid breast nodules. We performed a retrospective review of female patients who underwent breast surgery or puncture, aiming to establish a predictive model for evaluating the clinical malignancy risk of solid breast nodules. METHOD: Multivariable logistic regression was used to identify independent variables and establish a predictive model based on a model group (207 nodules). The regression model was further validated using a validation group (112 nodules). RESULTS: We identified six independent risk factors (X3, boundary; X4, margin; X6, resistive index; X7, S/L ratio; X9, increase of maximum sectional area; and X14, microcalcification) using multivariate analysis. The combined predictive formula for our model was: Z=-5.937 + 1.435X3 + 1.820X4 + 1.760X6 + 2.312X7 + 3.018X9 + 2.494X14. The accuracy, sensitivity, specificity, missed diagnosis rate, misdiagnosis rate, negative likelihood ratio, and positive likelihood ratio of the model were 88.39%, 90.00%, 87.80%, 10.00%, 12.20%, 7.38, and 0.11, respectively. CONCLUSION: This predictive model is simple, practical, and effective for evaluation of the malignancy risk of solid breast nodules in clinical settings.

Polysaccharide from vinegar baked radix bupleuri as efficient solubilizer for water-insoluble drugs of Chinese medicine.

The development of solubilizers with high efficiency, high safety and simple technology is one of the important fields in modern pharmaceutical industry. Our previous study found that vinegar baked Radix Bupleurum polysaccharides (VBCP) was a potential candidate. This study aimed to clarify which polysaccharide in VBCP had solubility enhancement effect and its solubilizing mechanism. Here, we reported that a novel acidic branched polysaccharide from VBCP, VBCP-3-A, which was non-toxic and had high solubility to baicalin and rhein. It was much better than that of Tween 80. The solubilization mechanism might be that VBCP-3-A self-assembled to form micelle-like aggregates in water, which can encapsulate water-insoluble constituents through the interaction of both hydrogen bonding and hydrophobic forces. in vivo pharmacokinetic study showed that VBCP-3-A increased Cmax and AUC (0-t) of baicalin and rhein. Those results suggested that VBCP-3-A was a potential solubilizer with high efficiency and high safety.

A Case of Pure Mucinous Breast Carcinoma in a 25-Year-Old Female Who Showed Complete Pathological Response to Neoadjuvant Chemotherapy despite Poor Clinical Response.

INTRODUCTION: Mucinous breast carcinoma is a rare histologic subtype of primary breast cancers accounting for 1-6%. It is a rare histological variant in young patients and usually presents without lymph node involvement, and its pathological response to neoadjuvant chemotherapy is rarely reported. CASE PRESENTATION: Pure mucinous breast carcinoma in a 25-year-old female was treated with neoadjuvant chemotherapy every 3 weeks for 8 cycles. After the fifth cycle, the mass size showed no change. We performed modified radical mastectomy in the left breast and axillary lymph node clearance. However, the pathological report showed a complete elimination of both the breast tumor and axillary lymph nodes, which were filled with mucus but did not contain malignant cells. DISCUSSION: Chemotherapy was profoundly effective against the tumor cells, but ineffective against large amounts of extracellular mucus. Even though the cancer cells were sensitive to chemotherapy, the volume of mucinous cancer couldnot be reduced. CONCLUSION: In summary, the evaluation criteria of tumor response to chemotherapy based on maximum diameter only should be considered insufficient for mucinous carcinoma.

Efficacy of Ultrasound-guided Radiofrequency Ablation of Parathyroid Hyperplasia: Single Session vs. Two-Session for Effect on Hypocalcemia.

To evaluate safety and efficacy of one- vs. two-session radiofrequency ablation (RFA) of parathyroid hyperplasia for patients with secondary hyperparathyroidism (SHPT) and to compare the outcome of both methods on hypocalcemia. Patients with secondary hyperparathyroidism underwent ultrasound guided RFA of parathyroid hyperplasia. Patients were alternately assigned to either group 1 (n = 28) with RFA of all 4 glands in one session or group 2 (n = 28) with RFA of 2 glands in a first session and other 2 glands in a second session. Serum parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) values were measured at a series of time points after RFA. RFA parameters, including operation duration and ablation time and hospitalization length and cost, were compared between the two groups. Mean PTH decreased in group 1 from 1865.18 ± 828.93 pg/ml to 145.72 ± 119.27 pg/ml at 1 day after RFA and in group 2 from 2256.64 ± 1021.72 pg/ml to 1388.13 ± 890.15 pg/ml at 1 day after first RFA and to 137.26 ± 107.12 pg/ml at 1 day after second RFA. Group 1's calcium level decreased to 1.79 ± 0.31 mmol/L at day 1 after RFA and group 2 decreased to 1.89 ± 0.26 mmol/L at day 1 after second session RFA (P < 0.05). Multivariate analysis showed that hypocalcemia was related to serum ALP. Patients with ALP ≥ 566 U/L had lower calcium compared to patients with ALP < 566 U/L up to a month after RFA (P < 0.05). Group 1's RFA time and hospitalization were shorter and had lower cost compared with Group 2. US-guided RFA of parathyroid hyperplasia is a safe and effective method for treating secondary hyperparathyroidism. Single-session RFA was more cost-effective and resulted in a shorter hospital stay compared to two sessions. However, patients with two-session RFA had less hypocalcemia, especially those with high ALP.

A preliminary study on the expression and clinical value of platelet-derived growth factor BB, hypoxia inducible factor-1α and C-C motif chemokine receptor-2 in peripheral blood during the pathogenesis of Graves' disease.

INTRODUCTION: Platelet-derived growth factor BB (PDGF-BB) plays an important role in the development of GD (Graves' disease). However, it is still unknown whether PDGF-BB is expressed in peripheral blood and whether the expression of PDGF-BB contributes to GD. We aim to study the expression of PDGF-BB, hypoxia inducible factor (HIF)-1α and C-C motif chemokine receptor (CCR)-2 in peripheral blood of patients with GD and explore its effect and potential mechanism in pathogenesis. MATERIAL AND METHODS: 41 patients with GD (GD group) and forty-five healthy people (control group) were chosen. The concentration of PDGF-BB and HIF-1α in peripheral blood specimens were detected and compared between the two groups. The expression of CCR2 in macrophages in the peripheral blood specimens were examined using FCM (Flow Cytometry). RESULTS: Both PDGF-BB and HIF-1α were expressed in human peripheral blood from the two groups. Compared with specimens from healthy people, there were statistically increased concentrations of PDGF-BB and HIF-1α in the GD group (P < 0.05). The proportion of CCR2-positive macrophages in peripheral blood in the GD group was significantly higher than that in the control group (P < 0.05). CONCLUSIONS: CCR2-positive macrophages may induce the expression of PDGF-BB through HIF-1α signal, and the high expression of PDGF-BB may be involved in the pathogenesis of GD.

Author Correction: Diagnostic value of ultrasound features and sex of fetuses in female patients with papillary thyroid microcarcinoma.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Diagnostic value of ultrasound features and sex of fetuses in female patients with papillary thyroid microcarcinoma.

Little work has been done on the prediction of papillary thyroid microcarcinoma in female patients who have given birth to children, which may be different from other people. We performed a retrospective review of female patients who underwent thyroidectomy, aiming at identifying special predictors of papillary thyroid microcarcinoma in female patients who have given birth to children. Univariate analysis was used to identify potential covariates for the prediction of papillary thyroid microcarcinoma. Multivariable logistic regression analysis was used to identify independent predictors and construct a regression model based on a training cohort (246 patients) and then the regression model was validated using an independent cohort (80 patients). We found that having not more than one boy, taller-than-wide shape, poorly defined margin, marked hypoechogenicity, and microcalcification were independent risk factors for the papillary thyroid microcarcinoma in multivariate analyses. The combined predictive formula had a high predictive effect for papillary thyroid microcarcinoma (AUC = 0.938 for training cohort and 0.929 for validation cohort, respectively). The combined predictive formula has clinical value in the prognosis of papillary thyroid microcarcinoma and it may be simple and effective to ask fertility condition of patients to increase the US diagnosis accuracy of papillary thyroid microcarcinoma.

Diaminosulfide based polymer microparticles as cancer vaccine delivery systems.

The aim of the research presented here was to determine the characteristics and immunostimulatory capacity, in vivo, of antigen and adjuvant co-loaded into microparticles made from a novel diaminosulfide polymer, poly(4,4'-trimethylenedipiperdyl sulfide) (PNSN), and to assess their potential as cancer vaccine vectors. PNSN microparticles co-loaded with the antigen, ovalbumin (OVA), and adjuvant, CpG 1826, (PNSN(OVA + CpG)) were fabricated and characterized for size (1.64 µm diameter; PDI=0.62), charge (-23.1 ± 0.3), and loading efficiencies of antigen (7.32 µg/mg particles) and adjuvant (0.95 µg/mg particles). The ability of PNSN(OVA + CpG) to stimulate cellular and humoral immune responses in vivo was compared with other PNSN microparticle formulations as well as with poly(lactic-co-glycolic acid)(PLGA)-based microparticles, co-loaded with OVA and CpG (PLGA(OVA + CpG)), an adenovirus encoding OVA (Ad5-OVA), and OVA delivered with incomplete Freund's adjuvant (IFA(OVA)). In vivo OVA-specific IgG1 responses, after subcutaneous prime/boosts in mice, were similar when PNSN(OVA + CpG) and PLGA(OVA + CpG) were compared and the presence of CpG 1826 within the PNSN microparticles demonstrated significantly improved responses when compared to PNSN microparticles loaded with OVA alone (PNSN(OVA)), plus or minus soluble CpG 1826. Cellular immune responses to all particle-based vaccine formulations ranged from being negligible to modest with PNSN(OVA + CpG) generating the greatest responses, displaying significantly increased levels of OVA-specific CD8+ T lymphocytes compared to controls and IFA(OVA) treated mice. Finally, it was shown that of all vaccination formulations tested PNSN(OVA + CpG) was the most protective against subsequent challenge with an OVA-expressing tumor cell line, E.G7. Thus, microparticles made from poly(diaminosulfide)-based macromolecules possess promising potential as vaccine vectors and, as demonstrated here, may have impact as cancer vaccines in particular.

Effect of receptor solution specific conductivity on iontophoresis of tetracaine hydrochloride.

AIM: To examine the quantitative relationship between solution specific conductivity and the permeability of tetracaine HCl, and to investigate the effect of receptor solution specific conductivity on the iontophoretic transport. METHODS: An in vitro study was carried out to determine the iontophoretic permeability of tetracaine hydrochloride through rat skin. Iontophoretic flux of tetracaine hydrochloride through excised rat skin was determined using Valia-Chien two-chamber diffusion cells with a constant d.c. current and Ag/AgCl electrodes. The specific conductivities of donor and receptor solution were also measured. RESULTS: Iontophoretic flux of tetracaine hydrochloride increased with a decrease of anion (chloride ion) concentration in receptor. And the iontophoretic permeability (ER, ER is the enhancement ratio, and ER = iontophoretic flux/passive flux) for tetracaine hydrochloride was directly related to the conductivity of receptor solution when other conditions were held constant. Linear regressions confirmed that ER was related to inverse of overall specific conductivity of donor and receptor solution [1/(ks.d + ks.r), ks.d and ks.r are the specific conductivity of donor and receptor solution]. CONCLUSION: The results suggest that specific conductivity of receptor solution may be a important factor for the iontophoretic permeability of a solute.

[Preparation of interferon-alpha-containing liposomes by the powder bed grinding method]

OBJECTIVE: To investigate a nwe, simple technique for preparation of interferon-alpha-liposomes, which may be suitable for industrial use. METHODS The uniform design coupled with computerized optimization was utilized to screen the formulation and preparation procedure of interferon-alpha-liposomes. Pro-liposomes were prepared by the powder bed grinding method and combined with interferon-alpha-solution to form interferon-alpha-liposomes. Liposome size was determined by the particle size analyzer. Free interferon-alpha and interferon-alpha-liposome were separated by gel filtration. Then the recovered activity of interferon-alpha was analyzed by enzyme-linked immunosorbent assay. RESULTS The result demonstrated that the best interferon-alpha-liposome formulation was as follows: the protectant was sorbitol; weight ratio of protectant to lipid was 5:1; weight ratio of octadecytamin to lipid was 1:9; weight ratio of sobey phosphatidylcholine to cholesterol was 9:1 respectively. Interferon-alpha-liposome size determined by the particle size analyzer was 80.8+/-36 nm and the encapsulation efficiency was 59.0+/-3.3%. CONCLUSION The powder bed grinding method can be used to prepare pro-liposomes which can be easily combined with interferon-alpha-solution to form interferon-alpha-liposomes.

[In vitro dexamethasone release from nanoparticles and its pharmacokinetics in the inner ear after administration of the drug-loaded nanoparticles via the round window].

OBJECTIVE: To investigate the feasibility of local drug delivery into the inner ear using solid lipid nanoparticles (SLN) and evaluate its potential for inner ear disease treatment in terms of the pharmacokinetics of the delivered drug in the inner ear. METHODS: Dexamethasone acetate (DA)-loaded SLN was prepared with Compritol 888 ATO as the matrix by means of hot dispersion-ultrasonic technique. A high-performance liquid chromatography (HPLC) was established for determining DA and dexamethasone (Dex). The pharmaceutical properties of DA-loaded SLN including the particle size, entrapment ratio and in vitro release were estimated. DA-loaded SLN was administered via intratympanic injection or intravenous injection in guinea pigs and Dex concentration in the perilymph was measured with HPLC for estimation of the pharmacokinetic parameters. RESULTS: The mean diameter of the DA-loaded SLN was 106.8 nm with entrapment ratio of 83.8%, and the in vitro DA release from the nanoparticles well conformed to Weibull distribution, with sustained-release of DA from the SLN exceeding 6 days. After intravenous injection of DA-loaded SLN in guinea pigs, Dex failed to be detected in the perilymph. Compared with Dex-loaded in situ gel following intratympanic injection, the relative bioavailability of Dex in the perilymph was 504% following intratympanic injection of DA-loaded SLN, which also resulted in increased t(1/2) and mean residence time (MRT) by 0.5 and 1.9 folds respectively. CONCLUSION: Nanoparticles can be a promising tympanic drug delivery system for topical drug administration in the treatment of inner ear diseases.