Effective targeted therapy for drug-resistant infection by ICAM-1 antibody-conjugated TPGS modified ß-Ga2O3:Cr3+ nanoparticles.

The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared ß-Ga2O3:Cr3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga2O3) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods: I-TPGS/Ga2O3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga2O3/TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga2O3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga2O3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga2O3/TIG were finally evaluated using acute pneumonia mice. Results: It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga2O3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo. Additionally, targeted delivery of I-TPGS/Ga2O3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion: It is of great value to apply I-TPGS/Ga2O3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.

Tocopherol polyethylene glycol succinate-modified hollow silver nanoparticles for combating bacteria-resistance.

Multiple drug resistance and the increase in the appearance of superbugs together with the exceedingly scant development of new potent antibiotic drugs pose an urgent global medical threat and imminent public security crisis. In the present study, we fabricated well-dispersed tocopherol polyethylene glycol succinate (TPGS)-capped silver nanoparticles (AgNPs) of about 10 nm in size. The hollow structure of the TPGS-capped AgNPs (TPGS/AgNPs) was confirmed and applied to load antibiotics. The TPGS/AgNPs proved to be able to cross the bacterial cell wall and penetrate into bacteria, thereby delivering more of the antibiotic to the interior of bacteria and thus enhancing the in vitro antibacterial effect of the antibiotic, even overcoming the drug-resistance in drug-resistant E. coli and Acinetobacter baumannii. It was found that the TPGS modification in the TPGS/AgNPs could decrease the activity of the efflux pumps AdeABC and AdeIJK in drug-resistant Acinetobacter baumannii via inhibiting the efflux pump genes adeB and adeJ, thus increasing the accumulation of the delivered antibiotic and overcoming the drug-resistance. Tigecycline delivered by TPGS/AgNPs could effectively antagonize drug-resistance in an acute peritonitis model mice, thereby increasing the survival rate and alleviating the inflammatory response. TPGS/AgNPs were developed as a novel and effective antibiotic delivery system and TPGS was demonstrated to have great potential as a pharmaceutical excipient for use in drug-resistant infection therapy.

CD44-targeted hyaluronic acid-curcumin prodrug protects renal tubular epithelial cell survival from oxidative stress damage.

Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H2O2-pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease.

Off-label prescriptions in intensive care unit: the Chinese experience.

BACKGROUND AND PURPOSE: Off-label prescriptions for critically ill patients pose several ethical and legal dilemmas for intensive care unit (ICU) clinicians. Yet, few data are available on the prevalence of this practice in critical care environment in China. This nationwide survey was performed to evaluate the conditions of off-label prescriptions in ICU within China. METHODS: The survey was performed at the scene of the national ICU conferences in 2016. ICU clinicians attending the congress from 23 provinces across the country were invited. The features of the clinician's off-label prescription practice were investigated and analyzed. RESULTS: A total of 1,318 ICU clinicians completed the anonymous questionnaire. Of these, 76.2% prescribed off-label in clinical practice. A significant difference (p<0.005) was observed between the ICU clinicians with different years of working experience and professional levels, respectively. For 69.2% of the ICU clinicians, the proportion of off-label prescriptions did not exceed 10%, while for fewer prescribers (2.9%), the proportion exceeded 25%. The main reasons for off-label prescriptions were life-threatening or terminal medical condition without other substitutes (48.3%), new treatments with strong scientific evidence (38.1%), and limited indications of drug labels (22.7%). Of the ICU clinicians surveyed, 87.5% worried about causing medical disputes, and 26.5% encountered medical disputes caused by off-label prescriptions. The risk of medical disputes was positively associated with the proportion of off-label prescriptions (p=0.009). Among the ICU clinicians, 92.5% expected the national policy for off-label prescriptions in future. Gastrointestinal and respiratory drug classes were noted to have the highest prevalence of off-label use. CONCLUSION: Off-label prescriptions have been commonly practiced by ICU clinicians in China. A concerted effort should be made to develop a practical and explicit guidance for off-label prescriptions.

E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury.

The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewisx antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DXM is incorporated into the micelles with 6.28 ± 0.21% drug loading content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to 48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to PEG-DXM micelles due to specific interaction between SA and E-selectin expressed on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can significantly ameliorate LPS-induced production of pro-inflammatory cytokines via suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM micelles show better therapeutical effects, as reflected by the improved renal function, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins.

Effectiveness of continuous improvement by a clinical pharmacist-led guidance team on the prophylactic antibiotics usage rationality in intervention procedure at a Chinese tertiary teaching hospital.

BACKGROUND: Irrational prophylactic antibiotics usage (PAU) during intervention procedures is common in China. A clinical pharmacist-led guidance team (CPGT) was established and participated in medical teams to advise on the rational usage of antibiotics. OBJECTIVES: The objective of this study was to assess the effectiveness of CPGT intervention for the rationality of PAU during intervention procedures. METHOD: This was a retrospective cross-sectional study with three stages at a Chinese tertiary teaching hospital. Patients who received some specific intervention procedures in the first quarter of 2015 were enrolled as the preintervention group, while those who received the procedures in the second and third quarters of 2015 were enrolled as the postintervention group. CPGT established the criteria for the PAU and conducted the intervention. The pre- and postintervention groups were then compared to evaluate the effectiveness of CPGTs' sustained interventions. RESULTS: A total of 651 patients were enrolled, with 200 patients in the preintervention group, while 233 patients and 218 patients in the first- and second-intervention groups, respectively. With the implementation of CPGTs continuous intervention, the rationality of PAU was significantly improved, including the timing (91.98% vs 97.74%, P=0.015), duration (82.72% vs 98.31%, P<0.0001), and choice (81.48% vs 93.22%, P=0.001) of antibiotics administered during perioperative period. Moreover, the cost of total (US$34.89±80.96 vs US$9.81±26.31, P=0.025) and inappropriate PAU (US$28.75±73.27 vs US$3.57±14.62, P<0.0001) per patient was significantly reduced. CONCLUSION: CPGTs' continuous intervention significantly improved the rationality of PAU during intervention procedures, with a significant reduction in antibiotic cost.

Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy.

Acute lung injury (ALI) is a critical illness without effective therapeutic modalities currently. Recent studies indicated potential efficacy of statins for ALI, while high-dose statins was suggested to be significant for attenuating inflammation in vivo. Therefore, a lung-targeted drug delivery system (DDS) delivering simvastatin (SV) for ALI therapy was developed, attempting to improve the disease with a decreased dose and minimize potential adverse effects. SV-loaded nanostructured lipid carriers (SV/NLCs) with different size were prepared primarily. With particle size increasing from 143.7 nm to 337.8 nm, SV/NLCs showed increasing drug-encapsulated efficiency from 66.70% to 91.04%. Although larger SV/NLCs exhibited slower in vitro cellular uptake by human vascular endothelial cell line EAhy926 at initial stage, while in vivo distribution demonstrated higher pulmonary accumulation of the larger ones. Thus, the largest size SV/NLCs (337.8 nm) were conjugated with intercellular adhesion molecule 1 (ICAM-1) antibody (anti-ICAM/SV/NLCs) for lung-targeted study. The anti-ICAM/SV/NLCs exhibited ideal lung-targeted characteristic in lipopolysaccharide-induced ALI mice. In vivo i.v. administration of anti-ICAM/SV/NLCs attenuated TNF-α, IL-6 and inflammatory cells infiltration more effectively than free SV or non-targeted SV/NLCs after 48-h administration. Significant histological improvements by anti-ICAM/SV/NLCs were further revealed by H&E stain. Therefore, ICAM-1 antibody-conjugated NLCs may represent a potential lung-targeted DDS contributing to ALI therapy by statins.

Inappropriateness of medication prescriptions about chronic kidney disease patients without dialysis therapy in a Chinese tertiary teaching hospital.

BACKGROUND: With the increasing incidence rate of chronic kidney disease (CKD), inappropriate use of medicine in CKD patients is an important issue, as it may cause adverse effects in patients and progression to chronic renal failure. OBJECTIVE: The aim of this study is to assess the frequency of inappropriate medicine use among CKD patients. METHODS: A cross-sectional study was conducted from November 1 to December 1, 2014 in a Chinese teaching tertiary hospital. All medication prescriptions for CKD patients with serum creatinine level above normal value were enrolled. The prescriptions, including unreasonable dosage, contraindicated, and cautiously used medicines in CKD patients, were evaluated and the related medications were also analyzed and classified. RESULTS: Two hundred and two patients were included, and a total of 1,733 lines of medication prescriptions were evaluated. The prevalence of inappropriate medication prescriptions in CKD patients was 15.18%, of which, unreasonable dosage (n=56), contraindicated (n=46), and cautiously used medicines (n=161) accounted for 3.23%, 2.65%, and 9.29%, respectively. Spearman's rank correlation coefficient implied that there was a significant correlation between the severity of renal insufficiency and frequency of inappropriate medication prescriptions (P=0.02, r=0.056). Among the inappropriate medication prescriptions, nutraceutical and electrolytes (n=65, 24.71%), cardiovascular drugs (n=61, 23.19%), and antimicrobial drugs (n=55, 20.91%) represented the top three medicine categories in CKD patients. CONCLUSION: The study confirmed that inappropriate medication prescriptions were prevalent in CKD patients. Improving the quality of medication prescriptions in CKD patients is necessary.

Effect of statins on the mortality and mechanical ventilation duration of acute lung injury patients: a meta-analysis of five randomized controlled trials.

BACKGROUND: Statins have been reported to exert anti-inflammatory effects, but the association between statins and acute lung injury (ALI) remains controversial. Thus, we performed a meta-analysis of all published randomized controlled trials (RCTs) aiming to summarize and evaluate the current evidence about the potential use of statins in ALI patients. METHOD: We searched for articles that focused on the association between statins and ALI-related outcomes through electronic databases until December 10th, 2014. The inclusion of articles, quality appraisal of included studies, and data extraction were performed by two investigators. Eligible articles were analyzed by Review manager 5.2 and STATA 12.0 software. RESULTS: Data from 1,778 patients in five randomized controlled clinical trials were analyzed. No differences in intensive care unit (ICU) mortality (RR=0.88, 95% CI=0.63-1.22, p=0.44), hospital mortality (RR=1.00, 95% CI=0.85-1.17, p=0.97) and mechanical ventilation duration (MD=-0.40, 95% CI=-1.52-0.71, p=0.48) were observed between the experimental and control groups. CONCLUSIONS: According to large and high-quality published clinical trials as also summarized by the present meta-analysis, there is insufficient evidence to support the use of statins in ALI patients.

Implementation of pharmacists' interventions and assessment of medication errors in an intensive care unit of a Chinese tertiary hospital.

BACKGROUND: Pharmacist interventions and medication errors potentially differ between the People's Republic of China and other countries. This study aimed to report interventions administered by clinical pharmacists and analyze medication errors in an intensive care unit (ICU) in a tertiary hospital in People's Republic of China. METHOD: A prospective, noncomparative, 6-month observational study was conducted in a general ICU of a tertiary hospital in the People's Republic of China. Clinical pharmacists performed interventions to prevent or resolve medication errors during daily rounds and documented all of these interventions and medication errors. Such interventions and medication errors were categorized and then analyzed. RESULTS: During the 6-month observation period, a total of 489 pharmacist interventions were reported. Approximately 407 (83.2%) pharmacist interventions were accepted by ICU physicians. The incidence rate of medication errors was 124.7 per 1,000 patient-days. Improper drug frequency or dosing (n=152, 37.3%), drug omission (n=83, 20.4%), and potential or actual occurrence of adverse drug reaction (n=54, 13.3%) were the three most commonly committed medication errors. Approximately 339 (83.4%) medication errors did not pose any risks to the patients. Antimicrobials (n=171, 35.0%) were the most frequent type of medication associated with errors. CONCLUSION: Medication errors during prescription frequently occurred in an ICU of a tertiary hospital in the People's Republic of China. Pharmacist interventions were also efficient in preventing medication errors.

Improving antimicrobial dosing in critically ill patients receiving continuous venovenous hemofiltration and the effect of pharmacist dosing adjustment.

BACKGROUND: Appropriate antimicrobial dosing for patients receiving continuous venovenous hemofiltration (CVVH) is complex. Pharmacist participation in antimicrobial dosing adjustment for patients receiving CVVH may be advantageous. METHODS: A comparative study was performed in a China hospital intensive care unit (ICU).Patients receiving CVVH in the intervention group received antimicrobial dosing adjustment service by pharmacists from January 2012 to June 2012, whereas patients in the control group received routine medical care between July 2012 and December 2012. The primary outcomes including patients' length of ICU stay, mortality in ICU, ICU hospitalization costs, and the occurrence of adverse drug events (ADEs) were then compared. RESULTS: 87 and 93 patients were included in the control and intervention groups. During the intervention period, pharmacists made 256 antimicrobial dosing adjustment recommendations for 93 enrolled patients receiving CVVH, of which 224 (87.5%) recommendations were accepted by physicians. Changing in CVVH-related variables (175, 68.4%) were the most common risk factors for dosing errors, whereas ß-lactams (131, 51.2%) were the most frequency of antimicrobials associated with dosing errors. Compared with the control group, pharmacist dosing adjustment resulted in £1637.7 cost savings per patient, and 2.36 times reduction of antimicrobial-related adverse drug events (ADEs) (11 vs 26, P=0.002), while length of ICU stay and mortality in ICU showed no significant difference (P>0.05). CONCLUSIONS: The involvement of pharmacist to participate in the ICU team rounds for patients receiving CVVH is associated with cost savings and reduction of ADEs. Hospital may consider employing ICU pharmacists.

Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study.

BACKGROUND: The impact of continuous renal replacement therapy (CRRT) on drug removal is complicated; pharmacist dosing adjustment for these patients may be advantageous. This study aims to describe the development and implementation of pharmacist dosing adjustment for critically ill patients receiving CRRT and to examine the effectiveness of pharmacist interventions. METHODS: A comparative study was conducted in an intensive care unit (ICU) of a university-affiliated hospital. Patients receiving CRRT in the intervention group received specialized pharmacy dosing service from pharmacists, whereas patients in the no-intervention group received routine medical care without pharmacist involvement. The two phases were compared to evaluate the outcome of pharmacist dosing adjustment. RESULTS: The pharmacist carried out 233 dosing adjustment recommendations for patients receiving CRRT, and 212 (90.98%) of the recommendations were well accepted by the physicians. Changes in CRRT-related variables (n=144, 61.81%) were the most common risk factors for dosing errors, whereas antibiotics (n=168, 72.10%) were the medications most commonly associated with dosing errors. Pharmacist dosing adjustment resulted in a US$2,345.98 ICU cost savings per critically ill patient receiving CRRT. Suspected adverse drug events in the intervention group were significantly lower than those in the preintervention group (35 in 27 patients versus [vs] 18 in eleven patients, P<0.001). However, there was no significant difference between length of ICU stay and mortality after pharmacist dosing adjustment, which was 8.93 days vs 7.68 days (P=0.26) and 30.10% vs 27.36% (P=0.39), respectively. CONCLUSION: Pharmacist dosing adjustment for patients receiving CRRT was well accepted by physicians, and was related with lower adverse drug event rates and ICU cost savings. These results may support the development of strategies to include a pharmacist in the multidisciplinary ICU team.

Impact of pharmacist antimicrobial dosing adjustments in septic patients on continuous renal replacement therapy in an intensive care unit.

BACKGROUND: Correct dosing of antimicrobial drugs in septic patients receiving continuous renal replacement therapy (CRRT) is complex. This study aimed to evaluate the effects of dosing adjustments performed by pharmacists on the length of intensive care unit (ICU) stay, ICU cost, and antimicrobial adverse drug events (ADEs). METHODS: A single-center, 2-phase (pre-/post-intervention) study was performed in an ICU of a university-affiliated hospital. Septic patients receiving CRRT in the post-intervention phase received a specialized antimicrobial dosing service from critical care pharmacists, whereas patients in the pre-intervention phase received routine medical care without involving pharmacists. The 2 phases were compared to evaluate the outcomes of pharmacist interventions. RESULTS: Pharmacists made 183 antimicrobial dosing adjustment recommendations for septic patients receiving CRRT. Changes in CRRT-related variables (116, 63.4%) were the most common risk factors for dosing errors, and ß-lactams (101, 55.2%) were the antimicrobials most commonly associated with dosing errors. Dosing adjustments were related to a reduced length of ICU stay from 10.7 ± 11.1 days to 7.7 ± 8.3 days (p = 0.037) in the intervention group, and to cost savings of $3525 (13,463 ± 12,045 vs. 9938 ± 8811, p = 0.038) per septic patient receiving CRRT in the ICU. Suspected antimicrobial adverse drug events in the intervention group were significantly fewer than in the pre-intervention group (19 events vs. 8 events, p = 0.048). CONCLUSIONS: The involvement of pharmacists in antimicrobial dosing adjustments in septic patients receiving CRRT is associated with a reduced length of ICU stay, lower ICU costs, and fewer ADEs. Hospitals may consider employing clinical pharmacists in ICUs.

Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin.

PURPOSE: Safe and effective lipid nanoemulsion (LNE) formulations for the antitumor delivery of doxorubicin is designed. METHODS: LNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEG)ylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated. Based on in-vitro cytotoxicity and cellular uptake tests of A549 (human lung carcinoma) cells, in-vivo biodistribution, antitumor activity, and cardiac toxicity are further examined using nude mouse bearing A549 tumor. RESULTS: The LNE size decreases from 126.4 ± 8.7 nm to 44.5 ± 9.3 nm with increased weight ratio of medium-chain triglyceride to soybean oil from 1:4 to 3:2, whereas the encapsulation efficiency of doxorubicin is slightly reduced from 79.2% ± 2.1% to 71.2% ± 2.9%. The PEGylation of LNE by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(PEG)2000] (DSPE-PEG 2000) does not significantly change the size and drug encapsulation efficiency. Three-month storage at room temperature and lyophilization process does not affect the drug encapsulation efficiency, whereas the size slightly increases to almost 100 nm. The in-vitro drug-release profiles of LNEs suggest that the present formulation can prolong drug release for 48 hours. LNEs can be internalized into tumor cells in vitro and efficiently accumulate in tumor tissues in vivo by passive targeting. Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced. CONCLUSION: The present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin.

Effectiveness of pharmaceutical care in an intensive care unit from China. A pre- and post-intervention study.

OBJECTIVE: To describe the development and implementation of pharmaceutical care services in an in-patient setting, and to examine the effectiveness of pharmacist interventions. METHODS: A single-center, 2-phase (pre-/post-intervention phase) design was performed in an intensive care unit (ICU) of a university-affiliated hospital. Patients in the post-intervention phase (March 2011 to June 2011) received pharmaceutical care from a clinical pharmacist, while patients in the pre-intervention phase (December 2010 to March 2011) received routine medical care. The pre- and post-intervention phases were then compared to evaluate the outcomes of pharmacist interventions. RESULTS: During the 3-month study period, the clinical pharmacist made 232 interventions for 416 admitted patients; of these, 202 (87.1%) were accepted by physicians or nurses, and dosage adjustment (n=83, [35.8%]) was the type of intervention implemented most often. In the group that received the participation of pharmacists, medication errors per patient decreased from 1.68 to 0.46 (p<0.001); medication errors, of incorrect dose or dosing interval, were markedly improved (decreased from 0.87 to 0.14; p<0.001), the drug cost per patient-day decreased from $347.43 to $307.36 (p=0.095), and the length of ICU stay did not change significantly (6.14 days versus 5.93 days; p=0.14). CONCLUSION: The presence of the pharmacist in the ICU resulted in significant reduction of medication errors and had potential drug-cost-saving effects, but did not have an influence on decreasing the length of ICU stay.

Strategic approaches for improving entrapment of hydrophilic peptide drugs by lipid nanoparticles.

In order to introduce hydrophilic peptide drugs into solid lipid nanoparticles (SLN), a technique of combining hydrophobic ion pairing (HIP) and non-aqueous oil-in-oil (O/O) emulsion-evaporation was developed. Leuprolide (LR) was selected as the model drug, while sodium stearate (SA-Na) was used as the negative charged ion pairing material. The formation of leuprolide-sodium stearate (LR-SA-Na) complex was confirmed by differential scanning calorimetry (DSC). It was observed that when the molar ratio of SA-Na/LR reached 2/1, ca 88.5% LR was incorporated into the hydrophobic ion complexes with SA-Na. Compared with the conventional method of solvent diffusion in an aqueous system, the efficiency of LR drug entrapment with SLN increased from 28.0% to 74.6% by the combined technique of HIP and O/O emulsion-evaporation. In vitro drug release tests revealed that employing technique of HIP obviously reduced the burst release and slowed down the rate of drug release. At meanwhile, applying the method of non-aqueous O/O emulsion-evaporation, the longer time of drug release but relatively higher drug burst release ratio was observed in comparison with those by the solvent diffusion method in an aqueous system. The drug entrapment and release behaviors of LR-SA-Na SLN prepared by the O/O emulsion-evaporation method suggested that it could potentially be exploited as an oral delivery system for leuprolide.

Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy.

Herein, solid lipid nanoparticles (SLN) were proposed as a new drug delivery system for adefovir dipivoxil (ADV). The octadecylamine-fluorescein isothiocynate (ODA-FITC) was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15. The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system. About 15 wt% drug entrapment efficiency (EE) and 3 wt% drug loading (DL) could be reached in SLN loading ADV. Comparing with free ADV, the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels in vitro were significantly enhanced.

Preparation and characteristics of monostearin nanostructured lipid carriers.

Nanostuctured lipid carriers (NLC) consisted of solid lipid and liquid lipid are a new type of lipid nanoparticles, which offer the advantage of improved drug loading capacity and release properties. In this study, solvent diffusion method was employed to produce NLC. Monostearin (MS) and caprylic/capric triglycerides (CT) were chosen as the solid lipid and liquid lipid. Clobetasol propionate used as a model drug was incorporated into the NLC. The influences of preparation temperature and CT content on physicochemical properties of the NLC were characterized. As a result, monostearin solid lipid nanoparticles (without CT content, SLN) obtained at higher temperature (70 degrees C) exhibited slightly higher drug loading capacity than that of 0 degrees C (P < 0.05). In contrast, the production temperature made little effect on NLC drug loading capacity (P > 0.05). The improved drug loading capacity was observed for NLC and it enhanced with increasing the CT content in NLC. The results were explained by differential scanning calorimetry (DSC) measurement for NLC. The incorporation of CT to NLC led to crystal order disturbance and thus left more space to accommodate drug molecules. NLC displayed a good ability to reduce the drug expulsion in storage compared to SLN. The in vitro release behaviors of NLC were dependent on the production temperature and CT content. NLC obtained at 70 degrees C exhibited biphasic drug release pattern with burst release at the initial 8h and prolonged release afterwards, whereas NLC obtained at 0 degrees C showed basically sustained drug release throughout the release time. The drug release rates were increased with increasing the CT content. These results indicated that the NLC produced by solvent diffusion method could potentially be exploited as a carrier with improved drug loading capacity and controlled drug release.