To improve the oral bioavailability of silymarin, the silymarin-loaded amphiphilic chitosan micelles (SM-OGC) were prepared. The absorption of SM-OGC in rat intestine was investigated. SM-OGC was prepared by dialysis method. The size and zeta potential of SM-OGC were investigated. Compared to silymarin suspension, the absorption of SM-OGC was investigated using in situ single pass perfusion model. The diameters and zeta potential SM-OGC were (162.4 +/- 3.0) nm and (+32.6 +/- 0.98) mV, respectively. The encapsulation efficiency was (39.17 +/- 0.98)% and the drug loading of SM-OGC was (28.15 +/- 0.43)%. The absorption of SM-OGC at different segments of intestine was significantly higher than that of silymarin suspension (P < 0.05). The apparent absorption rate (K(a)) and effective permeation coefficient (P(eff)) at the duodenum were the largest. K(a) and P(eff) had no significant difference between jejunum, ileum and colon. OGC micelles might significantly promote the absorption of silymarin in the intestine tract.
Animals ; Chitosan ; Colon ; metabolism ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Micelles ; Rats ; Rats, Sprague-Dawley ; Silymarin ; administration & dosage ; chemical synthesis ; pharmacokinetics

AIMTo prepare paclitaxel-loaded cationic chitosan micelles (PTX-CCM) and paclitaxel-loaded anionic chitosan micelles (PTX-ACM) and study the influence of surface charges on the biodistribution of paclitaxel-loaded chitosan polymeric micelles in mice.

METHODSPTX-CCM and PTX-ACM were prepared by dialysis method and were administered to mice by caudal vein at a dose of 20 mg x kg(-1) body weight. The RP-HPLC method was established to determine the PTX concentrations in the plasma and other tissues of mice. The tissues distribution of PTX-CCM and PTX-ACM were evaluated by the pharmacokinetic parameters (AUC, MRT).

RESULTSThe diameter and zeta potential of PTX-CCM were 164 nm and +23.7 mV, while those of PTX-ACM were 180 nm and -28.0 mV, respectively. The drug loading and drug encapsulation efficiency for PTX-CCM were 26.4% (w/w) and 76.2% , while those of PTX-ACM were 34.6% (w/w) and 89.9%, respectively. The highest uptake of PTX-CCM and PTX-ACM in liver were 64.72% and 91.84% of dose, respectively. Meanwhile, MRT of both were 5.50 h and 51.39 h prolonged. The highest uptake of PTX-CCM and PTX-ACM in spleen were 7.08% and 5.16% of dose, respectively. Meanwhile, MRT of both were 9.04 h and 26.82 h. For PTX-CCM group, the AUC and C(max) of PTX in the lung were 2.71 times and 5.87 times of those of PTX-ACM group respectively. While in both PTX-CCM and PTX-ACM groups, the highest uptake of PTX in the heart were only 0.36% and 0.24% of dose, respectively and PTX in the kidney were only 0.75% and 0.33% of dose respectively.

CONCLUSIONPTX-CCM and PTX-ACM showed excellent drug loading capabilities with amount of cationic charges and anionic charges on their surface, respectively. Both PTX-CCM and PTX-ACM groups showed a higher targeting efficiency in the liver and spleen in vivo and accumulated in both tissues for relatively long time, especially in PTX-ACM group. In contrast to PTX-ACM, PTX-CCM showed a higher lung targeting efficiency in vivo while PTX-ACM had a stronger retention ability in the lung. Meanwhile in both groups the levels of PTX in the heart and kidney tissues were significantly lower which might decrease the side effects of PTX.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; pharmacokinetics ; Area Under Curve ; Chitosan ; chemistry ; Delayed-Action Preparations ; Drug Delivery Systems ; Female ; Liver ; metabolism ; Lung ; metabolism ; Mice ; Micelles ; Paclitaxel ; administration & dosage ; chemistry ; pharmacokinetics ; Particle Size ; Spleen ; metabolism ; Surface Properties ; Tissue Distribution

To prepare doxorubicin-loaded N-octyl-N'-succinyl chitosan polymeric micelle (DOX-OSC) and study the biodistribution of DOX-OSC in mice, DOX-OSC was prepared by dialysis method. By using doxorubicin injection (DOX-INJ) as control, DOX-OSC and DOX-INJ were administered to mice through caudal vein at a dose of 5 mg x kg(-1) body weight. The RP-HPLC method was established to determine the DOX levels in the plasma and other tissues of mice. The tissues distribution and targeting efficiency were evaluated by pharmacokinetic parameters (AUC, MRT) and targeting parameters (Re, Ce and Te). The drug loading and entrapment efficiency of DOX-OSC were (35.8 +/- 0.4)% and (75.3 +/- 1.1)%, respectively. The diameter and zeta potential of DOX-OSC were (174 +/- 12) nm and (-37.1 +/- 3.0) mV, respectively. The transmission electron microscope result showed DOX-OSC with spherical shape. The biodistribution results showed that the concentration of DOX of both DOX-OSC and DOX-INJ decreased rapidly in blood after iv administration. While free DOX levels in blood at 12-96 h were not detectable for DOX-INJ, in contrast, DOX level in blood at 96 h was still found for DOX-OSC. In contrast to DOX-INJ group, DOX-OSC showed a higher targeting efficiency in the liver and spleen. The AUCs of DOX in the liver and spleen were 20.0 and 47.4 times and the MRT were 11.2 and 37.2 times, respectively. And the levels of DOX-OSC in the heart and kidney tissues were significantly reduced. And the drug distribution of DOX-OSC in the heart and kidney tissues were 17.0% and 11.4%, respectively. Hence, DOX-OSC shows an excellent drug loading capabilities and a higher targeting efficiency in the liver and spleen. That the levels of DOX-OSC in the heart and kidney tissues are significantly reduced, might improve the treatment efficacy of DOX and decrease the side effects.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Chitosan ; analogs & derivatives ; chemistry ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Female ; Liver ; metabolism ; Male ; Mice ; Micelles ; Particle Size ; Polymers ; Spleen ; metabolism ; Tissue Distribution

A series of novel self-assembled polymeric micelles based on carboxymethyl chitosan bearing long chain alkyl chains (N-octyl-O, N-carboxymethyl chitosan, OCC) was synthesized. PTX loaded OCC polymeric micelles (PTX-OCC) were prepared by dialysis method. The effects of the degree of substitutions (DS) of octyl groups on the solubilizing abilities of OCC for paclitaxel were studied. The PTX-OCC were characterized using drug loading content, drug encapsulation efficiency, dynamic light scattering, zeta potential and transmission electron microscopy (TEM). Take PTX injection (PTX-INJ) as control, the safety of PTX-OCC including hemolysis, hypersensitiveness in guinea pigs and acute toxicity in mice were also evaluated. OCC showed excellent loading capacities for paclitaxel with the DS of octyl groups in the range of 37.9% - 58.6%. Drug loading contents were up to 24.9% - 34.4% with drug encapsulation efficiency 56.3% - 89.3%, which both increased with the increasing of DS of octyl groups. The mean size of PTX-OCC was 186.4 - 201.1 nm which decreased with the increasing of DS of octyl groups. The zeta potential was -47.5 to -50.9 mV, which had no obvious relation with the DS of octyl groups. The TEM images showed a spherical shape. No burst release phenomena were observed and drug cumulative release was in the range of 60% -95% in 15 days. PTX-OCC with higher DS of octyl groups showed stronger sustained releasing ability. In terms of the induction of membrane damage and hypersensitiveness, PTX-OCC was superior to PTX-INJ. The LD50 and its 95% confidence interval of PTX-OCC were 134.4 (125.0 - 144.6) mg x kg(-1), which was 2.7 fold of PTX-INJ. The present PTX-OCC could be potentially useful as safety carriers for intravenous delivery.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; toxicity ; Chitosan ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Female ; Guinea Pigs ; Hemolysis ; drug effects ; Humans ; Hypersensitivity, Immediate ; chemically induced ; Male ; Mice ; Micelles ; Nanoparticles ; Paclitaxel ; administration & dosage ; pharmacology ; toxicity ; Particle Size ; Polymers

OBJECTIVETo investigate the prevalence and the risk factors of retinopathy of prematurity (ROP).

METHODSTotally 172 premature infants who were less than 37 weeks postconceptional age, or more than 37 weeks but weighing < 2 500 g at birth, and born at PUMC hospital from May 1, 2003 to November 30, 2004, were enrolled in this study. Their fundus were routinely checked. Diagnosis and staging of ROP were performed according to the international guidelines. Another 20 mature infants were selected as the control group.

RESULTSTwelve infants quitted the treatment or died. The remaining 160 infants completed the follow up. The prevalence of ROP in the premature group was 19.4%, while no ROP was found in the control group. The prevalence of ROP in subgroup with body weight < or = 2 000 g (28.4%) was significantly higher than in subgroup with body weight > 2 000 g (8.3%, chi2 = 10.217, P = 0.001) at birth. The prevalence of ROP in subgroup with postconceptional age < or = 32 weeks (42.5%) was significantly higher than in subgroup with postconceptional age > 32 weeks (11.7%, chi2 = 18.258, P = 0.000). The postconceptional age (OR = 0.959, P = 0.036) and body weight (OR = 0.999, P = 0.026) were the most important risk factors of ROP. Furthermore, blood transfusion ( OR = 0.076, P = 0.029) and Apgar score ( OR = 23.62, P = 0.012) were inversely correlated with ROP. Correlation was not found between ROP prevalence and oxygen inhalation mode, surface active substance, administration of dopamine and dexamethasone, and mother conditions.

CONCLUSIONSThe prevalence of ROP is higher in premature infants than in mature infants. Shorter postconceptional age and lower body weight may result in higher ROP incidence. Routine screening of fundus in premature infants may be helpful for the early detection of ROP.

Apgar Score ; China ; epidemiology ; Female ; Gestational Age ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Male ; Neonatal Screening ; Oxygen Inhalation Therapy ; adverse effects ; Prevalence ; Retinopathy of Prematurity ; epidemiology ; Risk Factors

Objective:To explore the carrier status of group B streptococci (GBS) in pregnant women of Mongolian and Han nationality and the neonatal GBS infection in order to identify the high risk factors of GBS infection in Mongolian and Han newborns in this area.Methods:Totally 7289 pregnant women and their newborns born alive were tested for GBS in the Affiliated Hospital of Inner Mongolia Medical University from June 2017 to June 2020, and their newborns were cultured for GBS, and the venous blood of newborns delivered by GBS positive women were detected for anti-GBS capsular polysaccharide antibody level, in order to determine the high risk factors of neonatal GBS infection.Results:Among the 7289 pregnant women, 3136 were Mongolian pregnant women (2599 full-term delivery and 537 premature delivery) and 4153 were Han pregnant women (3541 full-term delivery and 612 premature delivery). The results of GBS test showed that the GBS carrier rate was 8.19% in the Mongolian preterm delivery group, 4.35% in the Mongolian term group, 11.93% in the Han preterm group, and 5.76% in the Han term group, indicating that the carrier rate of GBS in the preterm group was significantly higher than that in the term group, regardless of Mongolian and Han nationality ( P < 0.05). Further comparing the GBS carrier rate of Mongolian and Han pregnant women, the GBS carrier rate of Mongolian pregnant women was significantly lower than that of Han pregnant women regardless of the premature delivery group and term group ( P < 0.05). (2) A total of 434 newborns were born by GBS positive parturients. The positive rates of GBS in Mongolian premature infants, Mongolian full-term infants, Han premature infants and Han full-term infants were 29.55%, 14.16%, 31.51% and 17.65%, respectively, suggesting that the positive rate of GBS in premature infants was significantly higher than that in full-term infants, regardless of Mongolian and Han nationality ( P<0.05). Further comparing the positive rate of GBS in Mongolian and Han newborns, there was no significant difference in the positive rate of GBS between Mongolian newborns and Han newborns, no matter the premature delivery group and the full-term group. (3) This study compared the incidence of early-onset GBS septicemia in Mongolian and Han newborns. The results showed that the incidence of early-onset GBS septicemia in Mongolian premature infants was 23.08%, and none in full-term infants. The incidence of early-onset GBS septicemia in Han premature infants was 26.09%. The incidence of early-onset GBS septicemia in term infants was 5.56%. The incidence of neonatal GBS septicemia in the preterm group was significantly higher than that in the term group, regardless of Mongolian and Han nationality. By further comparing the incidence of GBS septicemia in Mongolian and Han newborns, there was no significant difference in the positive rate of GBS between Mongolian newborns and Han newborns regardless of the premature delivery group and the term group. (4) In both Mongolian and Han nationality, the level of anti-GBS capsular polysaccharide antibody in premature infants was significantly lower than that in term infants ( P < 0.05). (5) Regardless of the Mongolian and Han nationality, compared with GBS negative group, GBS positive rate was higher in pregnant women aged≥35 years old, with history of menstruation, miscarriage, vaginitis, floating population, and those who had not undergone pre-pregnancy examination,,which were the high risk factors for GBS-positive pregnant women during pregnancy. (6) In both Mongolian and Han nationality, the incidence of chorioamnionitis, puerperal infection, premature delivery and premature rupture of membranes in the GBS positive group was higher than that in the GBS negative group, and the incidence of fetal distress and neonatal asphyxia in the GBS positive group was also higher than that in the GBS negative group. Conclusions:The carrier rate of GBS in Mongolian pregnant women is lower than that in Han pregnant women, and positive GBS during pregnancy will increase the incidence of adverse maternal and fetal outcomes such as chorioamnionitis, puerperal infection, premature delivery, premature rupture of membranes, fetal distress, neonatal asphyxia and neonatal early-onset GBS septicemia. The high risk factors are maternal age ≥ 35 years old, history of menstruation, abortion, vaginitis, floating population, and infection without pre-pregnancy examination. We should attach great importance to the perinatal high risk factors and formulate corresponding intervention measures accordingly, and make rational use of antibiotics for prenatal prevention, so as to further reduce the incidence of early-onset GBS septicemia in newborns.

OBJECTIVETo investigate the cut-off value in screening of thalassemia in pregnant women from Shenzhen region by capillary hemoglobin electrophoresis.

METHODSThe data of capillary hemoglobin electrophoresis and genetic diagnosis of thalassemia from 2122 examined prenatal women were retrospectively analyzed. Capillary hemoglobin electrophoresis and α-, β- genetic diagnosis of thalassemia were carried out for every woman. Hemoglobin electrophoresis was performed using Capillarys 2 full-automated electrophoresis instrument. Gap polymerase chain reaction and reverse dot blot were used for genetic diagnosis of thalassemia genotyping test. The cut-off value in screening of thalassemia was determined by receiver operating characteristic curve and next to analyze the value of HbA2 and HbF in screening of thalassemia using the decided cut-off value.

RESULTSThe areas under the curve (AUC(Roc)) of HbA2 for diagnosis of α-, β- thalassemia were 0.75 and 0.981 respectively, and the AUC(Roc) of HbF for diagnosis of β-thalassemia was 0.787. When HbA2 ≤ 2.55 was taken as the cut-off value of HbA2 for diagnosis of α-thalassemia, the sensitivity, specificity, positive likelihood ratio (LR(+)) and negative likelihood ratio (LR(-)) were 89.5%, 54.8%, 1.98, 0.19 respectively. When HbA2 ≥3.9 was taken as the cut off value of HbA2 for diagnosis of β-thalassemia, the sensitivity, specificity, LR(+) and LR(-) were 96.1%, 99.8% 480.5, 0.04 respectively. When HbF ≥0.75 was taken as the cut off value of HbF for diagnosis of β-thalassemia, the sensitivity, specificity, LR(+) and LR(-) were 83.6%, 61.8% respectively.

CONCLUSIONThe cut-off value in screening of thalassemia by capillarys 2 full automated electrophoresis instrument is different from that of the traditional method of hemoglobin electrophoresis, such as cellulose acetate membrane electrophoresis and agarose gel electrophoresis. Each laboratory should establish their own respective cut off value.

Area Under Curve ; China ; Electrophoresis, Capillary ; Female ; Fetal Hemoglobin ; analysis ; Genotyping Techniques ; Hematologic Tests ; Hemoglobin A2 ; analysis ; Humans ; Mass Screening ; Pregnancy ; Reference Values ; Retrospective Studies ; Sensitivity and Specificity ; alpha-Thalassemia ; diagnosis ; beta-Thalassemia ; diagnosis