Abstract：
:Effectiveness of CNS-acting drugs depends on the localization, targeting, and capacity to be transported through the blood-brain barrier (BBB) which can be achieved by designing brain-targeting delivery vectors. Hence, the objective of this study was to screen the formulation and process variables affecting the performance of sertraline (Ser-HCl)-loaded pegylated and glycosylated liposomes. The prepared vectors were characterized for Ser-HCl entrapment, size, surface charge, release behavior, and in vitro transport through the BBB. Furthermore, the compatibility among liposomal components was assessed using SEM, FTIR, and DSC analysis. Through a thorough screening study, enhancement of Ser-HCl entrapment, nanosized liposomes with low skewness, maximized stability, and controlled drug leakage were attained. The solid-state characterization revealed remarkable interaction between Ser-HCl and the charging agent to determine drug entrapment and leakage. Moreover, results of liposomal transport through mouse brain endothelialpolyoma cells demonstrated greater capacity of the proposed glycosylated liposomes to target the cerebellar due to its higher density of GLUT1 and higher glucose utilization. This transport capacity was confirmed by the inhibiting action of both cytochalasin B and phenobarbital. Using C6 glioma cells model, flow cytometry, time-lapse live cell imaging, and in vivo NIR fluorescence imaging demonstrated that optimized glycosylated liposomes can be transported through the BBB by classical endocytosis, as well as by specific transcytosis. In conclusion, the current study proposed a thorough screening of important formulation and process variabilities affecting brain-targeting liposomes for further scale-up processes.
journal_name
AAPS PharmSciTechjournal_title
AAPS PharmSciTechauthors
Harbi I,Aljaeid B,El-Say KM,Zidan ASdoi
10.1208/s12249-016-0481-7subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1404-1420issue
6issn
1530-9932pii
10.1208/s12249-016-0481-7journal_volume
17pub_type
杂志文章abstract：:The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilex...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-018-1129-6
更新日期：2018-10-01 00:00:00
abstract：:Cancerous invasion yields unusual metabolisms providing a significant amount of peptide albuminomes that modulate albumin stability via binding. The study aimed at the investigation of the thermal stability of human plasma albumin with breast cancer of various stages by means of differential scanning calorimetry (DSC)...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-019-1356-5
更新日期：2019-03-18 00:00:00
abstract：:This work was aimed at evaluating the effect of a pharmaceutical cationic exchange resin (Amberlite IRP-69) on the properties of controlled release matrices using Methocel K4M (HPMC) or Ethocel 7cP (EC) as matrix formers. Diphenhydramine hydrochloride (DPH), which was cationic and water soluble, was chosen as a model ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-008-9129-6
更新日期：2008-01-01 00:00:00
abstract：:Helicobacter pylori infection remains challenging as it mainly colonized beneath the deep gastric mucosa and adheres to epithelial cells of the stomach. Concanavalin-A (Con-A)-conjugated gastro-retentive poly (lactic-co-glycolic acid) (PLGA) nanoparticles of acetohydroxamic acid (AHA) and clarithromycin (CLR) were pre...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-015-0443-5
更新日期：2016-10-01 00:00:00
abstract：:The aim of this study was to formulate a new delivery system for ecological pesticides by the incorporation of Artemisia arborescens L essential oil into solid lipid nanoparticles (SLN). Two different SLN formulations were prepared following the high-pressure homogenization technique using Compritol 888 ATO as lipid a...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/pt070102
更新日期：2006-01-03 00:00:00
abstract：:As of March 10, 2020, more than 100,000 novel coronavirus pneumonia cases have been confirmed globally. With the continuous spread of the new coronavirus pneumonia epidemic in even the world, prevention and treatment of the disease have become urgent tasks. The drugs currently being developed are not adequate to deal ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章,评审
doi：10.1208/s12249-020-01679-z
更新日期：2020-05-13 00:00:00
abstract：:Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-012-9787-2
更新日期：2012-06-01 00:00:00
abstract：:The objective of this study was to investigate the combined effect of pH modifiers and nucleation inhibitors on enhancing and sustaining the dissolution of AMG 009 tablet via supersaturation. Several bases and polymers were added as pH modifiers and nucleation inhibitors, respectively, to evaluate their impact on the ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-011-9679-x
更新日期：2011-12-01 00:00:00
abstract：:An encapsulation of model drug raloxifene hydrochloride (RAL) inside the chitosan decorated pH responsive mesoporous system has a greater potential for accumulating in the tumor cells. The present study involves synthesis of surface modified mesoporous silica nanoparticles (MSN) with the aim of achieving pH sensitive ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-017-0949-0
更新日期：2018-04-01 00:00:00
abstract：:Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. T...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-016-0489-z
更新日期：2017-01-01 00:00:00
abstract：:Hard capsules are made from gelatin, an organic polymer obtained through the hydrolysis of collagen present in animal tissues. Gelatin can be degraded by microorganisms and some strategies can be used to control contaminating micro-organisms. Gamma irradiation is considered as an effective sterilization method; howeve...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-019-1394-z
更新日期：2019-05-20 00:00:00
abstract：:A dissolution test for tablets containing 40 mg of olmesartan medoxomil (OLM) was developed and validated using both LC-UV and UV methods. After evaluation of the sink condition, dissolution medium, and stability of the drug, the method was validated using USP apparatus 2, 50 rpm rotation speed, and 900 ml of deaerate...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-010-9421-0
更新日期：2010-06-01 00:00:00
abstract：:The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of w/o microemulsion (M) and gel (G) bases for diclofenac sodium (DS). The effect of dimethyl sulfoxide (DMSO) as a penetration enhancer was also examined when it was added to the M formulation. To study the in vitro poten...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/pt070488
更新日期：2006-10-20 00:00:00
abstract：:Paclitaxel (PTX) and gemcitabine (GEM) are often used in combination due to the synergistic anticancer effects. PTX and GEM combination showed a synergistic effect to SKOV-3 cells at a molar ratio of 1 to 1 and in PTX ➔ GEM sequence. Liposomes were explored as a carrier of PTX and GEM combination. We optimized the dru...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-017-0877-z
更新日期：2018-02-01 00:00:00
abstract：:Hypertension remains a significant risk factor for several cardiovascular disorders including coronary artery disease and heart failure. Despite the large armamentarium of drugs available for the management of high blood pressure, low oral availability is an ongoing challenge. Researchers are constantly developing alt...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章,评审
doi：10.1208/s12249-019-1583-9
更新日期：2020-01-06 00:00:00
abstract：:The impact of pharmaceutical materials properties on drug product quality and manufacturability is well recognised by the industry. An ongoing effort across industry and academia, the Manufacturing Classification System consortium, aims to gather the existing body of knowledge in a common framework to provide guidance...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章,评审
doi：10.1208/s12249-018-1198-6
更新日期：2018-11-01 00:00:00
abstract：:The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often ter...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-015-0308-y
更新日期：2015-10-01 00:00:00
abstract：:The release of propranolol hydrochloride from matrix tablets with hydroxy propyl methyl cellulose (HPMC K15M) or KollidonSR at different concentrations was investigated with a view to developing twice daily sustained release dosage form. A hydrophilic matrix-based tablet using different concentrations of HPMC K15M or ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-008-9092-2
更新日期：2008-01-01 00:00:00
abstract：:Top-spray fluidized bed granulation with axial fluidization airflow from the bottom of the granulator is well-established in the pharmaceutical industry. The application of swirling airflow for fluidized bed granulation was more recently introduced. This study examined the effects of various process parameters on the ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-012-9906-0
更新日期：2013-03-01 00:00:00
abstract：:Colorectal cancer is a global concern, and its treatment is fraught with non-selective effects including adverse side effects requiring hospital visits and palliative care. A relatively safe drug formulated in a bioavailability enhancing and targeting delivery platform will be of significance. Metformin-loaded solid l...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-016-0505-3
更新日期：2017-02-01 00:00:00
abstract：:Polymeric films are safe and effective and can be used for vaginal administration of microbicide drug candidates. Dapivirine (DPV), an investigational and clinically advanced antiretroviral drug, was selected as a model compound for this study. We have previously developed and clinically tested a quick-dissolving DPV ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-019-1442-8
更新日期：2019-06-26 00:00:00
abstract：:Multidrug resistance is the major problem in cancer treatment nowadays. Compounds from plants are the new targets to solve this problem. Quercetin (QCT), quercetrin (QTR), and rutin (RUT) are potential anticancer flavonoids but their poor water solubility leads to less efficacy. In this study, the polymeric micelles o...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-020-01657-5
更新日期：2020-04-26 00:00:00
abstract：:The scale up of production processes is a major challenge in pharmaceutical industry. Using a quality by design approach, upscaling can be based on the design space, which can be assessed on a small scale. In a previous study, the critical process parameters were identified by a definitive screening design on cetomacr...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-018-1063-7
更新日期：2018-07-01 00:00:00
abstract：:The purpose of this research was to develop and evaluate different preparations of sustained delivery systems, using Carbopols as carriers, in the form of matrices and three-layer tablets with isosorbite mononitrate. Matrix tablets were prepared by direct compression whereas three-layer tablets were prepared by compre...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-008-9084-2
更新日期：2008-01-01 00:00:00
abstract：:The purpose of this research was to use our previously validated dynamic injection apparatus as a rapid method for screening pH-adjusted formulations of a new vancomycin analog, Van-An, for their potential to precipitate upon dilution. In 1 vial, Van-An was reconstituted according to the manufacturer's instructions. I...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/pt070105
更新日期：2006-03-01 00:00:00
abstract：:The purpose of this study was to investigate the effect of particle size, storage temperature, and duration of storage on the physical stability and morphology of polylactic-co-glycolic acid (PLGA) nanospheres and microspheres. PLGA nanospheres and microspheres containing the fluorescent dye, Bodipy, were prepared in ...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/pt050453
更新日期：2004-09-13 00:00:00
abstract：:Hypertension shows circadian blood pressure rhythms (day-night pattern) that urge the delivery of antihypertensive drugs at the right time in the desired levels. Thus, a bilayered core-in-cup buccoadhesive tablet was formulated that immediately releases olmesartan, to give a burst effect, and controls azelnidipine rel...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-019-1575-9
更新日期：2019-12-10 00:00:00
abstract：:Formulation effects on the entrapment of beclometasone dipropionate (BDP) in liposomes generated by hydration of proliposomes were studied, using the high-density dispersion medium deuterium oxide in comparison to deionized water (DW). Proliposomes incorporating BDP (2 mol% of the lipid phase consisting of soya phosph...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-017-0793-2
更新日期：2018-01-01 00:00:00
abstract：:The purpose of the study was to synthesize and characterize a new form of topical membranes as chitosan-based hydrogel membranes for bacterial skin infections. The polymeric membranes were synthesized by modification in free radical solution polymerization technique. High molecular weight (HMW) chitosan polymer was cr...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-018-1131-z
更新日期：2018-10-01 00:00:00
abstract：:The purpose of this research was to address the utility of rheological study in understanding the influence of oppositely charged polymers on release of naproxen sodium encapsulated in chitosan particles. The interaction between oppositely charged kappa-carrageenan (kappa-Ca) and chitosan leads to relatively higher ge...
journal_title：AAPS PharmSciTech
pub_type： 杂志文章
doi：10.1208/s12249-010-9379-y
更新日期：2010-03-01 00:00:00
