Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.     

Survival Estimates for Patients with Abnormal Swallowing Studies

OBJECTIVE: To better understand the life expectancy of patients who have an abnormal videofluoroscopic swallowing study. DESIGN: Retrospective cohort study. The common starting point was the time of the severely abnormal swallowing study. Hospital charts were reviewed for clinical variables of potential prognostic significance by reviewers blinded to the outcome of interest, survival time. SETTING: A university-affiliated, community teaching hospital. PATIENTS: One hundred forty-nine hospitalized patients who were deemed nonoral feeders based on their swallowing study. Patients excluded were those with head, neck, or esophageal cancer, or those undergoing a thoracotomy procedure. MEASUREMENTS AND MAIN RESULTS: Clinical and demographic variables and time until death or censoring were measured. Overall 1-year mortality was 62%. Multivariable Cox proportional hazards analyses identified four variables that independently predicted death: advanced age, reduced serum albumin concentration, disorientation to person, and higher Charlson comorbidity score. Eighty patients (54%) subsequently underwent placement of a percutaneous endoscopic gastrostomy (PEG) tube after their swallowing study. CONCLUSIONS: Mortality is high in patients with severely abnormal swallowing studies. Common clinical variables can be used to identify groups of patients with particularly poor prognoses. This information may help guide discussions regarding possible PEG placement.     

Direct percutaneous endoscopic jejunostomy: a case series in pediatric patients.

BACKGROUND: Direct percutaneous endoscopic jejunostomy (DPEJ) is a well-known approach to deliver postpyloric enteral nutrition support to individuals who cannot tolerate gastric feeding. DPEJ addresses many of the shortcomings of jejunal feeding tubes placed through percutaneous endoscopic gastrostomy tubes. The safety and efficacy of DPEJ in adults has been previously reported. There are no reports on the use of DPEJ in pediatric patients. OBJECTIVE: Our purpose was to report on 5 pediatric patients who underwent DPEJ placement between January 2000 and January 2003 over the available follow-up periods. DESIGN: Retrospective case series. SETTING: University of Utah Health Sciences Center and the Medical University of South Carolina. PATIENTS: Five patients, age range 4 to 17 years. MAIN OUTCOME MEASUREMENTS: Rate of successful tube placement, major and minor complications, and outcomes including weight gain and recurrent aspiration after DPEJ placement. RESULTS: All 5 attempted DPEJs were placed successfully with 2 minor complications of peristomal leakage and peristomal skin infection. One DPEJ was replaced 2 years after placement because of fungal degradation. The mean weight gain among all patients was 10.3 kg in a mean of 22.6 months. LIMITATIONS: Retrospective, small series. CONCLUSIONS: DPEJ placement appears to be a safe and effective approach to enteral nutritional support in pediatric patients requiring long-term access to the jejunum. No major complications occurred and all patients gained weight after tube placement.     

Tablet formulation of Famotidine-loaded P-gp inhibiting nanoparticles using PLA-g-PEG grafted polymer

Our work aimed at evaluating the use of permeability glycoprotein (P-gp) inhibiting nanoparticles (NPs) as a part of a suitable oral solid dosage to improve bioavailability. Famotidine (Pepcid^®), a stomach acid production inhibitor, was used as a drug model to test our hypothesis. Famotidine-loaded NPs were prepared by solvent emulsion evaporation using PEG grafted on a polylactide acid (PLA) polymer backbone (PLA-g-PEG), with a 5% molar ratio of PEG versus lactic acid monomer and PEG of either 750 or 2000?Da molecular weight. Tablet formulation was composed of 40% Famotidine-loaded NPs, 52.5% microcrystalline cellulose as filler, 7% pre-gelatinized starch as binder/disintegrant, and 0.5% magnesium stearate as lubricant. Tablets containing 1.6?mg of Famotidine were prepared at an average weight of 500?mg, thickness of 6.2–6.5?mm, hardness of 5–8?kp, and disintegration time of <1?min. Our results suggest that Famotidine-loaded NPs using grafted PEG-g-PLA polymers can be formulated as an oral solid dosage form while effectively inhibiting P-gp mediated Famotidine efflux, irrespective of PEG molecular weights. This could therefore represent an attractive formulation alternative to enhance oral permeability and bioavailability of drugs that are P-gp substrates.     

Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM

Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon.     

Quantitative Prediction of Oral Bioavailability of a Lipophilic Antineoplastic Drug Bexarotene Administered in Lipidic Formulation Using a Combined In Vitro Lipolysis/Microsomal Metabolism Approach

For performance assessment of the lipid-based drug delivery systems (LBDDSs), in vitro lipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilization processes. Much of previous research on in vitro lipolysis has mostly focused on rank-ordering formulations for their predicted performances. In this study, we have incorporated in vitro lipolysis with microsomal stability to quantitatively predict the oral bioavailability of a lipophilic antineoplastic drug bexarotene (BEX) administered in LBDDS. Two types of LBDDS were applied: lipid solution and lipid suspension. The predicted oral bioavailability values of BEX from linking in vitro lipolysis with microsomal stability for lipid solution and lipid suspension were 34.2 ± 1.6% and 36.2 ± 2.6%, respectively, whereas the in vivo oral bioavailability of BEX was tested as 31.5 ± 13.4% and 31.4 ± 5.2%, respectively. The predicted oral bioavailability corresponded well with the oral bioavailability for both formulations, demonstrating that the combination of in vitro lipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivo intestinal lymphatic uptake was also assessed for the formulations and resulted in <1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability.     

下颈椎前路椎弓根螺钉固定系统与普通前路椎体螺钉固定系统的静力学比较

目的：比较下颈椎前路椎弓根螺钉（ATPS）锁定固定系统和普通前路椎体螺钉（VBS）锁定固定系统的静力学特性。方法：采集新鲜颈椎标本16具,分解为C3.,4,C4,5,C5,6,C6,7共32个运动节段（functionalspinalunit,FSU）,其中C3,4,C4,5,C5,6,C6,7各8个。将其按照不同节段随机分成A、B两组,对所获标本椎间盘切除后模拟植骨,分别植入自行设计生产的下颈椎前路椎弓根螺钉配套钢板系统和普通颈椎前路椎体螺钉钢板系统。在生物力学试验机上行钢板的垂直拔出强度试验。结果：下颈椎前路椎弓根螺钉的最大轴向拔出力为（604．68±48．76）N,椎体螺钉为（488．24±32．42）N,两者比较差异有统计学意义（t=2．147,P〈0．05）,前路椎弓根螺钉固定系统与椎体螺钉固定系统在各FSU间差异无统计学意义（A组和B组的F值分别为2．27、2．05,P〉0．05）。结论：下颈椎前路椎弓根螺钉钢板系统的拔出力明显优于普通前路椎体螺钉钢板系统,从生物力学角度上来看具有应用可行性。     

表面处理及不同水门汀材料对纤维桩粘固性能影响的研究

目的：评价酸蚀一喷砂处理以及4种不同水门汀材料Fuji I（FUI）、Fuji Cem（FUC）、RelyX Unicem（RX—U）、RelyXARC（RXA））对纤维桩粘固性能的影响。方法：选取80颗无龋坏单根管人前磨牙,根据对应纤维桩表面处理与否随机分为2组,进而根据粘接材料的不同分为4个亚组。常规根管充填和桩道预备后,分别选用4种水门汀材料将表面处理前后的玻璃纤维桩粘接到预备根管内;观察纤维桩表面及每组试件粘接界面扫描电镜（SEM）下微观形貌,测试即刻拉出强度（pull—outtest）。结果：表面处理前后纤维桩的各水门汀材料拉出强度以RXA组最高,随后依次为RXU、FUC、FUI组,且各组间均相差显著（P〈0．05）;纤维桩表面处理后与各水门汀材料的拉出强度较之处理前均显著提高（P〈0．05）：SEM观察显示：表面处理后纤维桩的表面粗糙度纤维暴露数量均有明显增加;表面处理前后各组粘接界面微观形貌存在差异,各组的粘接界面均较处理前更致密。结论：酸蚀一喷砂处理纤维桩表面后可以提高其与不同水门汀材料的粘接固位力。