Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1-BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

This study was performed to explore factors influencing the release of the proton pump inhibitor omeprazole from enteric-coated capsules in vitro and absorption in vivo in beagle dogs. Enteric-coated pellets with different enteric coating materials and coating levels were designed and prepared. All self-prepared formulations were characterized in vitro as well as in vivo and compared to the brand and generic commercial products. Evaluation of the corresponding release profiles suggested that coating material was the most critical factor. Enteric coating level determined the lag time before initiation of drug release, and subcoating level affected the drug release rate. Pharmacokinetic studies were performed in beagle dogs to further confirm the influence of formulation factors on drug absorption. Medium at pH 6.8 was a more biorelevant condition for in vitro drug release tests, although medium at pH 6.0 was better for discriminating release profiles of different formulations. A multiple level C in vitro/in vivo correlation was preliminarily established by which Tmax and Cmax of omeprazole formulations could be predicted with release parameters such as Tlag and T25. These results may facilitate quality evaluation and potentially improve the clinical efficacy of generic omeprazole products.

The purpose of this study was to solve the plateau phase (the stage in which the drug in the microsphere undergoes a slow release or almost no release after initial release) problem by understanding the effect of polymer blends on the internal pore changes of the microspheres. This study used PLGA 5050 4H (F-1), PLGA 5050 1A: PLGA 5050 4H = 3:7 (F-2) and PLGA 7525 1A: PLGA 5050 4H = 3:7 (F-3) as a carrier, respectively. Microspheres (MS) were obtained by O/W emulsion solvent evaporation technique and characterized by scanning electron microscopy (SEM), particle size, drug loading, fluorescence characteristics, and in vitro and in vivo release. Accelerated tests in vitro showed that the size and number of core pores significantly affected drug release in the first and second phases. After intramuscular administration, F-2 and F-3 showed effective blood concentration levels and their bioavailability was higher than that of the RLD (Sandostatin Lar). In general, our data indicate that pore formation is unevenly distributed throughout PLGA MS prepared using polymer blends, and the use of polymer blends is instructive for the development of sustained smooth release microspheres. Therefore, the octreotide MS described in this study has a good clinical application potential for the treatment of acromegaly.

In this work, the effect of β-sitosterol (Sito) on vesicle characteristics, physicochemical stability as well as the in vitro release and bioavailability of curcumin-loaded liposomes (Cur-LP) was studied. When 20-33 mol% of Sito was incorporated, encapsulation efficiency of curcumin was improved due to the high amount of liquid-ordered domains in membranes. At 50 mol% Sito a lower encapsulation efficiency was observed possibly due to membrane defects. The physical, thermal and photo stability of curcumin in liposomes were markedly improved with increasing the amount of Sito. First-order kinetics fitted best the curcumin release dynamics of Sito containing liposomes, clearly showing that sustained release improved with increasing amounts of Sito in liposomes. Simulated digestion studies suggested that Sito concentration of about 20-33 mol% improved the bioavailability of curcumin in liposomes. These study shows that Sito is an applicable and potential route in forming healthier cholesterol-free curcumin-loaded liposomes for functional supplements.

Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12 ± 0.72 nm, 0.183 ± 0.046, and -38.31 ± 0.33 mV, respectively, coupled with high encapsulation efficiency of 93.76 ± 0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.

The aim of the study was to investigate the high-sensitivity troponin T (hs-TnT) release profile in off-pump coronary artery bypass grafting (OPCABG) patients with normal postoperative course.
From January 2015 to October 2016, 398 consecutive OPCABG patients who had normal postoperative courses were enrolled. Blood samples for hs-TnT were collected at several time points and the comparisons among different time points grouped by various factors were further analyzed.
There were 317 male and 81 female patients, with a median age of 64. For 66.1% of the patients, peak hs-TnT occurred at the 24th hour after OPCABG, regardless of the groups divided by different factors. In total, the hs-TnT values were much higher in male group (P = 0.035), in patients who need 5 or more bypass grafts (P = 0.035) and in patients with high-risk EuroSCORE II assessment (P = 0.013). However, we failed to find any significant differences between different age groups (P = 0.129) or among different coronary heart disease classifications (P = 0.191).
The hs-TnT values were affected by various factors and culminated around the first 24 h following OPCABG. It may provide some useful information for future clinical studies of myocardial biomarkers after OPCABG.

Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control.

To fabricate thermo- and pH-sensitive hydrogels functionalized with β-cyclodextrin (β-CD) moieties, β-CD polymer bearing methacrylate (CDP-g-GMA) used as a reactive and functional crosslinker was synthesized, and then copolymerized with N-isopropylacrylamide (NIPAAm) and acrylic acid (AA) in aqueous solution via UV-initiated free radical polymerization. The stimulus-responsiveness of the resultant hydrogels has been carried out by measuring the swelling ratio at different temperatures and pH values. The results showed that the thermo- and pH-sensitivities of the produced hydrogels were significantly dependent on the compositions of the hydrogels, and the dual sensitivities exhibited good reversible process. The interior morphology observed by SEM exhibited that the pore size of the hydrogels could be tailored by pH of the local medium. Using a water-soluble cationic dye methyl violet (MV) as a model drug, MV loading and release profiles of the hydrogels as potential drug controlled release carriers were evaluated. The MV release rate from CD-functionalized hydrogels was much slower than that from the hydrogel without β-CDs at both pH 2.0 and pH 7.4. The release of MV from CD-functionalized hydrogels at pH 2.0 was faster than that at pH 7.4, the release kinetics of MV from the CD-functionalized hydrogels displayed a sustained release profile, and the release mechanism followed Fickian diffusion.

Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX(®) Sprinkle (RAB) delayed-release capsules (ACIPHEX(®) Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX(®) Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX(®) Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX(®) Sprinkle.

The efficacy of carbon nanotubes based drug delivery systems (DDSs) has long been compromised by low drug loading efficiency and rapid release profile, especially for drugs encapsulated inside nanotubes. To address these deficiencies, the large-inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) were employed to synthesize an innovative cisplatin (CDDP)-loaded DDS. A multi-step purification and oxidation procedure was developed to achieve ultrapurified oxidized LID-MWCNTs prior to entrapping CDDP. High molecular weight polyethylene glycol (PEG) was grafted onto the nanotubes to partially block the exit paths of drugs. As assessed by TGA and ICP-OES analyses, CDDP loading efficiency of resulting DDS was as high as 100.12%, and sustained release profile was obtained. Finally, the anticancer activity on CAL-27 cells was evaluated, and enhanced inhibition effect (IC50 values 3.93 μg/ml) was recorded. The successful inner-cavity-loading of LID-MWCNTs also provides a basis for establishing more complicated multi-functional DDSs.