Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Research progress of anti-tumor in situ gel delivery system / 药学学报

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

Effect of modified double-clamp procedure with preservation of Scarpa fascia in abdominoplasty / 中华医学美学美容杂志

Objective:To investigate the application of the modified double-clamp surgery with the preservation of Scarpa fascia in abdominoplasty.Methods:A retrospective analysis was carried out in 26 female patients with total abdominoplasty who were admitted from March 2020 to January 2022, ranging in age from 26 to 50 years with averaged 36.9 years. The patients were divided into flap clamp group (12 cases) and Scarpa fascia clamp group (14 cases). The surgical time of abdominoplasty (excluding liposuction time), the occurrence of postoperative seroma, and postoperative incision infection were recorded in the two groups.Results:The average surgical time of the patients in the Scarpa fascia clamp group was 136 minutes, which was significantly lower than that of the flap clamp group (153 minutes) ( P<0.05). There was no postoperative seroma and incision infection in the two groups, and the postoperative incision healing grades were I/A. Conclusions:The modified double-clamp procedure with preservation of the Scarpa fascia can effectively reduce the surgical time and improve the operation efficiency.

Efficacy, safety and cost-effectiveness of flow diverters in the treatment of intracranial aneurysms / 国际脑血管病杂志

Intracranial aneurysm is a common cerebrovascular disease. Its rupture causes subarachnoid hemorrhage with high mortality and disability. At present, the main treatment methods of intracranial aneurysms include craniotomy clipping and intravascular embolization. With the invention of flow diverters and wide application in clinic, it has gradually become another mainstream treatment method of intracranial aneurysms. This article reviews the effectiveness, safety and cost-effectiveness of flow diverters in the treatment of intracranial aneurysms.

Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area. @*Materials and Methods@#A total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression. @*Results@#The C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p< 0.001 for all). @*Conclusion@#These user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.

Study on endpoint determination method of tablet coating based on 3σ criteria and logic regression / 中国中药杂志

This paper explores the statistical distribution characteristics of coating film thickness, so as to present a new method for determining coating endpoint based on 3σ criterion and logic regression. Firstly, the spectrum and thickness of 4 batch samples were collected. Secondly, the spectral range of normal products was obtained by 3σ criterion, with the spectral feature NI as the number of test spectrum in the above range. Then, the model based on 3σ criterion and logic regression was built according to the best condition in K-fold cross-validation and the determined threshold of qualified rate in the coating endpoint. Finally, the qualified rate of test set samples at different time points was calculated by the above model, and the above change trend and the threshold value were combined to determine the coating endpoint. The results of KS analysis showed the distribution of thickness of the qualified products followed the normal distribution(P=0.081>0.05). The accuracy of the coating endpoint determination was as high as 100% by the model based on 3σ criterion and logic regression when the determined threshold of qualified rate was 90%. Therefore, the 3σ criterion was feasible to the research of coating eligibility. This paper reveals certain random phenomena in the coating process, and the method features a high accuracy, quick analysis and a good interpretability, which provides a reference for online detection and qualify evaluation in future.

Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area. @*Materials and Methods@#A total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression. @*Results@#The C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p< 0.001 for all). @*Conclusion@#These user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.

Advances in research on exosomes as drug delivery vehicles / 药学学报

Exosomes are membranous vesicles that are actively secreted by cells. They can be isolated from various cell culture media and animal body fluids. Exosomes are mainly composed of lipids, proteins and nucleic acids. They have small molecular structure and high biocompatibility with size of 40-100 nm. In addition, exosomes are natural endogenous nanocarriers that can transport lipids, proteins, DNA and RNA. Studies have shown that exosomes play an important role in long-distance communication between cells, in physiological and pathological processes. This article introduces the composition and physiological functions of exosomes, and summarizes the relevant content of exosomes as drug delivery vehicles. The applications of exosomes in central nervous system diseases, especially brain diseases and tumors are summarized.

Clinical characteristics and treatment courses for cytomegalovirus-associated thrombocytopenia in immunocompetent children after neonatal period

BACKGROUND: Cytomegalovirus (CMV) causes severe diseases in premature infants and immunocompromised hosts, and antiviral therapy is often required for disease control. However, the clinical manifestations and treatment courses for CMV-associated thrombocytopenia in immunocompetent children are unclear. METHODS: Medical records of the children who suffered from thrombocytopenia, and showed positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively analyzed at three university hospitals in Daegu from January 2000 to March 2017. Patients suffering from leukemia, immunodeficiency, and other infections were excluded. RESULTS: Among 1,065 children with thrombocytopenia, 29 (2.7%) displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15 months and the median platelet count was 26,000/µL. They were classified into the CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction, four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was used for 21 patients, and six patients among them showed recurrence, for whom IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for the CMV-related secondary ITP group (0/6); however, the results were not statistically significant (P=0.148). CONCLUSION: CMV is a rare but unique etiology of thrombocytopenia, and observed even in healthy children after the neonatal period. About one-third patients need antiviral therapy for disease control. Further, CMV-induced thrombocytopenia is more complex than CMV-related secondary ITP.

The effect of conditional knocking out vascular endothelial growth factor gene on the mouse model of oxygen induced retinopathy / 中华眼底病杂志

Objective To observe the effect of conditional knocking out (KO) vascular endothelial growth factor (VEGF) gene on the mouse model of oxygen induced retinopathy (OIR). Methods The conditional VEGF KO mice were generated using Cre-Loxp technology, resulting in the deletion of VEGF in a portion of Müller cells permanently in mouse retina. Cre positive was CKO mice, Cre negative was NKO mice. OIR was induced by keeping mice in 75% oxygen at postnatal 7 days (P7) to P12 and in room air from P12 to P17 (each 20 mice for CKO and NKO, respectively). The mice mortality was analyzed. At day P17, the percentage of retinal avascular area was calculated using retinal flat-mounting with fluorescence angiography, the number of vascular endothelial cell nucleus breaking through retinal inner limiting membrane was counted with hematoxylin eosin (HE) staining of retinal sections, and the expression of hypoxia-inducible factor-1α (HIF-1α) was detected by immunofluorescence analysis. Results During the development of OIR, the mortality rate of CKO mice (65.00%) was higher than that of NKO mice (30.00%) with the significant difference (x2=4.912, P=0.027). At day P17, all the mice retinas were harvested. The retinal fluorescence angiography displayed that the normal retinal vascularization of CKO mice was delayed, and large avascular areas were observed. Meanwhile, rare new vascular plexus was found in CKO mice and the thickness of whole retina decreased dramatically. In contrast, NKO mice developed larger area of normal retinal vascular network structure with higher blood vessel density and more new vascular plexus with obvious fluorescein leakage. The percentage of avascular area in CKO mice [(28.31±11.15)%] was higher than NKO mice [(16.82±7.23)%] with the significant difference (t=2.734,P=0.014). The HE staining of retinal sections indicated smaller counts of vascular endothelial cell nucleus breaking through retinal inner limiting membrane in CKO mice (26.10±6.37) when compared to NKO mice (28.80±7.59) , the difference was significant (t=2.437,P=0.016). The immunofluorescence analysis showed stronger expression of HIF-1α in CKO mice than NKO mice, which was mainly located in the retinal ganglion cell layer. Conclusions The local VEGF gene knockout partially inhibits retinal neovascularization in OIR mice. However, it also suppresses the normal retinal blood vascular development with a decrease of OIR mice survival ability.

The effect of conditional knocking out vascular endothelial growth factor gene on the mouse model of oxygen induced retinopathy / 中华眼底病杂志

Objective To observe the effect of conditional knocking out (KO) vascular endothelial growth factor (VEGF) gene on the mouse model of oxygen induced retinopathy (OIR). Methods The conditional VEGF KO mice were generated using Cre-Loxp technology, resulting in the deletion of VEGF in a portion of Müller cells permanently in mouse retina. Cre positive was CKO mice, Cre negative was NKO mice. OIR was induced by keeping mice in 75% oxygen at postnatal 7 days (P7) to P12 and in room air from P12 to P17 (each 20 mice for CKO and NKO, respectively). The mice mortality was analyzed. At day P17, the percentage of retinal avascular area was calculated using retinal flat-mounting with fluorescence angiography, the number of vascular endothelial cell nucleus breaking through retinal inner limiting membrane was counted with hematoxylin eosin (HE) staining of retinal sections, and the expression of hypoxia-inducible factor-1α (HIF-1α) was detected by immunofluorescence analysis. Results During the development of OIR, the mortality rate of CKO mice (65.00%) was higher than that of NKO mice (30.00%) with the significant difference (x2=4.912, P=0.027). At day P17, all the mice retinas were harvested. The retinal fluorescence angiography displayed that the normal retinal vascularization of CKO mice was delayed, and large avascular areas were observed. Meanwhile, rare new vascular plexus was found in CKO mice and the thickness of whole retina decreased dramatically. In contrast, NKO mice developed larger area of normal retinal vascular network structure with higher blood vessel density and more new vascular plexus with obvious fluorescein leakage. The percentage of avascular area in CKO mice [(28.31±11.15)%] was higher than NKO mice [(16.82±7.23)%] with the significant difference (t=2.734,P=0.014). The HE staining of retinal sections indicated smaller counts of vascular endothelial cell nucleus breaking through retinal inner limiting membrane in CKO mice (26.10±6.37) when compared to NKO mice (28.80±7.59) , the difference was significant (t=2.437,P=0.016). The immunofluorescence analysis showed stronger expression of HIF-1α in CKO mice than NKO mice, which was mainly located in the retinal ganglion cell layer. Conclusions The local VEGF gene knockout partially inhibits retinal neovascularization in OIR mice. However, it also suppresses the normal retinal blood vascular development with a decrease of OIR mice survival ability.

Pheochromocytoma Developed in a Boy with Multiple Endocrine Neoplasia Type 2A Confirmed by the RET Proto-Oncogene Mutation / 임상소아혈액종양

A 9-year-old boy presented with increased sweating and abdominal pain. His mother and uncle had been diagnosed with bilateral pheochromocytoma and medullary thyroid carcinoma. Magnetic resonance imaging of the boy's abdomen revealed a 7.5 cm×7.0 cm×6.0 cm mass with a thick peripheral enhancing wall and fluid-fluid level at the right suprarenal region. His ¹²³I-meta-iodobenzylguanidine (MIBG) scan showed a large mass with increased MIBG uptake in the right adrenal gland. The levels of serum norepinephrine, urine epinephrine/norepinephrine, metanephrine, and vanillylmandelic acid were elevated. He, his mother, and two sisters tested positive for the known mutation of multiple endocrine neoplasia type 2A, Cys634Tyr in RET proto-oncogene. Laparoscopic tumor excision and right adrenalectomy were performed. Final diagnosis was pheochromocytoma with malignant behavior, based on adrenal gland scoring scale. However, there was no overt metastasis. After surgery, his symptoms resolved and abnormal laboratory tests were normalized.

Study on the effect of massage therapy combined with medications on MGD / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To study the effect of tarsal gland massage combined with medication in treatment of meibomian gland dysfunction (MGD).METHODS:Totally 100 patients (189 eyes) with MGD were selected in our hospital from December 2014 to December 2016.The patients were randomly divided into control group and observation group.Patients in the control group were treated with routine drugs,while the patients in the observation group were treated with routine massage.We observed and compared the clinical efficacy of two groups of patients before treatment,1 wk,1 and 3mo after treatment for the subjective symptoms,tear film break-up time,tear secretion test,ocular surface disease index,corneal staining score of the patients in the 3 groups.RESULTS:The total effective rate of the observation group was 93.6％,which was significantly higher than that of the control group (P＜ 0.05).Two groups of patients after treatment of subjective symptoms,ocular surface disease index,corneal staining score decreased,tear break-up time,Schirmer test was increased compared with before treatment (P＜0.05).The decrease of subjective symptoms,ocular surface disease index,corneal staining score,the increase of tear film break-up time,tear secretion test in the observation group were higher than those in the control group (P＜0.05).CONCLUSION:Massage combined with medication can improve the clinical efficacy of MGD.

Lung Ultrasonography for the Diagnosis of Respiratory Distress Syndrome in Late Preterm Infants: Changing Incidence – A Single Center Experience

PURPOSE: Ultrasonography is non-ionizing, easy to operate, and performed at bedside in neonatal intensive care unit (NICU). We investigated the incidence of respiratory distress syndrome (RDS) with or without using lung ultrasound (LUS) in late preterm infants with postnatal respiratory difficulties. METHODS: We retrospectively reviewed medical records of 494 late preterm infants born at 34–36 weeks' gestation at Keimyung University Dongsan Medical Center. Fifty infants with postnatal respiratory difficulties were admitted to the NICU between May 2015 to October 2015 (period I), and forty-one were between November 2015 to February 2016 (period II). The diagnosis of RDS was based on chest radiography in period I. LUS was additionally performed at bedside in period II. All infants with RDS were received exogenous surfactant therapy. RESULTS: The overall incidence of RDS with surfactant replacement therapy was decreased in period II period II (9.4%, 20/212) compared to period I (14.5%, 41/282) (P=0.088). In terms of infants with postnatal respiratory difficulties, the incidence of RDS in period II (48.8%, 20/41) was significantly lower than that in period I (82.0%, 41/50) (P=0.001). There are no difference in the rate of reintubation, repeated doses of surfactant, oxygen demand at 48 hours after birth, air leak syndrome, pulmonary hemorrhage, persistent pulmonary hypertension of newborn, and mortality (P> 0.05). CONCLUSION: We could decrease the incidence of RDS with surfactant replacement therapy by using LUS in late preterm infants with postnatal respiratory difficulties. Further prospective studies are needed to apply LUS clinically to diagnose RDS.

Pheochromocytoma Developed in a Boy with Multiple Endocrine Neoplasia Type 2A Confirmed by the RET Proto-Oncogene Mutation / 임상소아혈액종양

A 9-year-old boy presented with increased sweating and abdominal pain. His mother and uncle had been diagnosed with bilateral pheochromocytoma and medullary thyroid carcinoma. Magnetic resonance imaging of the boy's abdomen revealed a 7.5 cm×7.0 cm×6.0 cm mass with a thick peripheral enhancing wall and fluid-fluid level at the right suprarenal region. His ¹²³I-meta-iodobenzylguanidine (MIBG) scan showed a large mass with increased MIBG uptake in the right adrenal gland. The levels of serum norepinephrine, urine epinephrine/norepinephrine, metanephrine, and vanillylmandelic acid were elevated. He, his mother, and two sisters tested positive for the known mutation of multiple endocrine neoplasia type 2A, Cys634Tyr in RET proto-oncogene. Laparoscopic tumor excision and right adrenalectomy were performed. Final diagnosis was pheochromocytoma with malignant behavior, based on adrenal gland scoring scale. However, there was no overt metastasis. After surgery, his symptoms resolved and abnormal laboratory tests were normalized.

The development of cell-penetrating peptides in drug delivery system / 药学学报

Cell membrane serves as the natural barrier. Cell-penetrating peptides (CPPs) have been a powerful vehicle for the intracellular delivery of a large variety of cargoes cross the cell membrane. The efficiency of intracellular delivery of drugs, proteins, peptides and nucleic acid, as well as various nanoparticu-late pharmaceutical carriers (e.g., liposomes, polymeric micelles and inorganic nanoparticles) has been demon-strated both in vitro and in vivo. This review focuses on the CPPs-based strategy for intracellular delivery of small molecule drugs, proteins, peptides, nucleic acid and CPP-modified nanocarriers.

Comparison on imaging features of central serous chorioretinopathy fundus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore and analyze the image features, diagnosis and treatment of the central serous chorioretinopathy ( CSCR) fundus. METHODS:From May 2008 to May 2014, 97 cases of 121 eyes with central serous chorioretinopathy were treated in in our hospital. The imaging features were compared and analyzed through different methods. RESULTS:Sixty-one cases (61 eyes) were ≤45 years, including 13 case with disease in both eyes, single stove leak accounted for 48. 6%, multifocal leakage (25. 7%), atypical leakage accounted for 25. 7%. Thirty-six cases (47 eyes) were >45 years, 11 cases with disease in both eyes, single focal leakage ( 8. 5%), multifocal leakage (48. 9%), atypical leakage accounted for 42. 6%. FFA results showed acute hairstyle at the beginning of 89 eyes, chronic deferment type 32 eyes. OCT examination showed that the main features were neuroepithelial detachment, as well as the change of the retinal pigment epithelium ( RPE) layer, which was divided into RPE layer detachment 93 eyes, accounting for 76. 9%, rough and RPE little ridges in 28 cases, accounting for 23. 1%. The average thickness of macular center concave on the cortex of microns was 137. 87 ± 19. 21μm, and there was no significant difference conpared with normal ( 137. 32 ±4.98μm) microns (t=0. 30, P>0. 05). The closer leakage area to macular fovea, the worse of eyesight. . CONCLUSION: Different imaging examination on central serous chorioretinopathy can show different features. For clinical diagnosis and treatment it had different and complementary roles, but were given significant help for diseases treatment.

Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles / 华中科技大学学报（医学）（英德文版）

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Development, characterization and in vitro evaluation of docetaxel-loaded polymeric micelles / 中国药学杂志

OBJECTIVE: To employ PEG-PCL diblock copolymers to prepare DTX-loaded polymeric micelles (PEG-PCL-DTX micelles, DTX-PMs) which addressed the issue of DTX's drug loading capacity, encapsulation efficiency and in vitro release. We also studied its effectiveness for the cytotoxicity on prostate cancer. METHODS: The polymeric micelles were screened by its shape using transmission electron microscope and were also characterized in terms of particle size, Zeta potential, drug loading efficiency, in vitro release and cytotoxicity by using laser particle size analyzer and HPLC. Cytotoxicity against LNCap-C4-2B prostate cancer cells of the DTX-PMs and commercial product of Duopafei® were evaluated by MTT assay. RESULTS: The average particle size and Zeta potential of DTX-PMs were found to be 25.1 nm and 0.64 mV. The micelles' drug loading and encapsulation efficiency were 8.72% and 98.1%, respectively. Cytotoxicity assay showed that DTX-PMs exerted significant anti-proliferation activity on LNCap-C4-2B prostate cancer cells. CONCLUSION: Slightly soluable DTX successfully formulated into the PEG-PCL micells, exhibiting small partical size and good stability. Delayed release in vitro and maintained quite a constant concentration in plasma for a long period, which was favorable for its clinic application. In conclusion, DTX-PMs developed here sufficiently solubilized DTX and increase the concentration of DTX in aqueous phase, offering a sustained in vitro release and effective cytotoxicity on LNCap-C4-2B prostate cancer.

Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles / 华中科技大学学报（医学）（英德文版）

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.