Abstract:
:Lipid nanoparticles (LNs) are widely investigated for oral drug delivery, and for achieving significant advantages in colloidal stability, biocompatibility and scaled-up possibility. However, researchers face challenge of developing methods to improve the ability of LNs in overcoming multiple barriers (i.e., mucus and epithelium barrier) in gastrointestinal (GI) tract because of the contradictory requirement of nanoparticle (NP) surface properties in the two processes. Therefore, we designed novel LNs with adjustable surface properties by coating lipid core with hydrophobic substitutes grafting N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA). In the present study, different substitutes (i.e., monocyclic, polycyclic, and linear segments) were grafted on pHPMA backbone. Screening studies demonstrated that type and grafting degree of substitutes both influenced hydrophilic-hydrophobic properties of NP surface and improved penetration through mucus. When a hydrophilic-hydrophobic balance was achieved, NPs showed elevated mucus permeability compared with bare LNs; this phenomenon subsequently contributed to higher cellular uptake. Moreover, β-sitosterol (SITO)-modified pHPMA-coated (grafting degree: 5%) LNs (5% SITO-LNs) exhibited the highest mucus permeability, transepithelial transport, and in situ absorption. Interestingly, even with the highest surface hydrophilicity, 5% SITO-LNs with Caco-2 cells did not show impaired membrane affinity, which was not observed in other groups. Further investigations of mechanism demonstrated that membrane affinity was significantly enhanced by β-SITO-mediated interaction with Niemann-Pick C1-like 1 (NPC1L1) protein on cell membranes. These results proved that hydrophobic substitutes play a critical role in altering hydrophilic-hydrophobic property of particle surface and improving penetration through multiple barriers. β-SITO-induced specific interaction can provide additional benefits to efficiency of oral delivery of LNs.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Wu L,Liu M,Shan W,Cui Y,Zhang Z,Huang Ydoi
10.1016/j.ijpharm.2017.02.015subject
Has Abstractpub_date
2017-03-30 00:00:00pages
216-227issue
1-2eissn
0378-5173issn
1873-3476pii
S0378-5173(17)30096-0journal_volume
520pub_type
杂志文章abstract::Dextran nanobubbles were prepared with a dextran shell and a perfluoropentan core in which oxygen was stored. To increase the stability polyvinylpirrolidone was also added to the formulation as stabilizing agent. Rhodamine B was used as fluorescent marker to obtain fluorescent nanobubbles. The nanobubble formulations ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2009.07.010
更新日期:2009-11-03 00:00:00
abstract::Subcutaneous vaccination of C57bl/6 mice with irradiated B16 melanoma cells supplemented with liposomal interleukin-2 (IL2) or murine interferon-gamma (mIFNgamma), resulted in systemic protection in 50% of the animals, against a subsequent tumor cell challenge in a dose dependent manner. The protective efficacy was co...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(99)00039-3
更新日期:1999-06-10 00:00:00
abstract::The aim of the present work was to develop a lymph targeted SLN formulation of antiretroviral (ARV) drug and to have an understanding of its underlying mechanism of uptake by the lymphatics. The lymphatics are the inaccessible reservoirs of HIV in human body. Efavirenz (EFV) is a BCS class II, ARV drug that undergoes ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.09.014
更新日期:2015-11-10 00:00:00
abstract::In order to protect protein and peptide drugs against inactivation by different barriers in the gastro-intestinal tract and to improve their absorption, alginate microparticles as a carrier of L-lactate dehydrogenase, were developed by spray-drying technique. However, alginate complexation and spray-drying conditions ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00171-0
更新日期:2002-08-21 00:00:00
abstract::Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the us...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.02.003
更新日期:2012-05-10 00:00:00
abstract::In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscop...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.118688
更新日期:2019-10-30 00:00:00
abstract::The development of vaccine delivery systems that will remove or reduce the need for repeated dosing has led to the investigation of sustained release systems. In this context, the duration of antigen release is of great importance as is the requirement for concomitant adjuvant release. In this work, lipid implants con...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.06.052
更新日期:2015-09-30 00:00:00
abstract::Hesperetin, an aglycone of the flavanone hesperidin, is a potential candidate for the treatment of diabetic retinopathy and macular edema. The purpose of this investigation was to determine solubility, stability and in vitro permeability characteristics of hesperetin across excised rabbit corneas. Aqueous and pH depen...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2010.04.036
更新日期:2010-07-15 00:00:00
abstract::Effects of pH and co-solvents on the bio-mimetic artificial membrane permeation assay were investigated to determine the optimal conditions for the prediction of oral absorption. The permeability (P(am)) of 33 structurally diverse drugs to the PC/PE/PS/PI/CHO/1,7-octadiene membrane system (bio-mimetic lipid (BML) memb...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00845-6
更新日期:2001-10-09 00:00:00
abstract::In the pharmaceutical industry, in vitro dissolution testing ofsolid oral dosage forms is a very important tool for drug development and quality control. However, ion-pairing interaction between the ionic drugand surfactants in dissolution medium often occurs, resulting in inconsistent and incomplete drug release. The...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.10.063
更新日期:2018-01-15 00:00:00
abstract::Polyamine content, which is associated with tumor growth, can be regulated by ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAMDC), two key enzymes in polyamine biosynthesis. Here we aim to develop a pH-responsive cationic poly(agmatine) based on a polyamine analogue-agmatine that can dually f...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.04.039
更新日期:2016-06-15 00:00:00
abstract::Mixing of raw materials (drug+polymer) in the investigated mini pharma melt extruder is achieved by using co-rotating conical twin screws and an internal recirculation channel. In-line Raman spectroscopy was implemented in the barrels, allowing monitoring of the melt during processing. The aim of this study was twofol...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.11.065
更新日期:2017-01-30 00:00:00
abstract::Nanocarriers may provide interesting delivery platforms for microbicide drugs and their characterization should be addressed early in development. Differently surface-engineered dapivirine-loaded, poly(epsilon-caprolactone) (PCL)-based nanoparticles (NPs) were obtained by nanoprecipitation using polyethylene oxide (PE...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.08.049
更新日期:2013-11-18 00:00:00
abstract::The effect of different formulation factors (lipid type, cholesterol, charge, internal buffer capacity, drug-to-lipid incubation ratio) on the encapsulation efficiency and size of primaquine liposomes (SUV's) in response to a pH gradient was investigated by a fractional factorial screen ing design. Three of the factor...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00338-0
更新日期:2000-04-05 00:00:00
abstract::The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were p...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.10.064
更新日期:2017-01-10 00:00:00
abstract::Cancer treatment combining chemotherapy and immunotherapy has been vigorously exploited to further improve cancer therapeutic efficacy. This study investigated a new chemoimmunotherapy approach utilizing hydrogel as a local anti-cancer drug delivery system. Chitosan hydrogel containing doxorubicin (CH-DOX) and vaccini...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2007.08.014
更新日期:2008-02-28 00:00:00
abstract::Microspheres of roxithromycin with Eudragit S100 and silica were prepared by the emulsion solvent diffusion method to mask the bitter taste of the antibiotic. The effect of different polymers and drug-polymer ratios on the taste masking and the characteristics of the microspheres were investigated. It was found that E...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.03.018
更新日期:2006-08-02 00:00:00
abstract::To facilitate targeting drug delivery and combined therapy, we develop titanium dioxide-encapsulated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs). Titanium dioxide (TiO2), which is employed as a sonosensitizer for sonodynamic therapy (SDT), can also be used for the loading of doxorubicin (DOX). The fabricated Fe3O4@TiO2 NPs e...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.03.070
更新日期:2015-01-01 00:00:00
abstract::The purpose of this study was to optimize in vitro experimental conditions for the measurement of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) permeation across human skin using a flow-through diffusion cell system. The drug permeation rates through intact and stripped (stratum corneum (SC) removed) skin were also com...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00262-4
更新日期:2002-07-25 00:00:00
abstract::Implantable polymeric device that can release chemotherapeutic agent directly into central nervous system (CNS) has had an impact on malignant glioma therapy. The purpose of our study was to develop an implantable polymeric device, which can release intact 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for long-term peri...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00543-4
更新日期:2003-01-30 00:00:00
abstract::The work was aimed at developing an in vitro method able to provide rapid and reliable evaluation of drug absorption through buccal mucosa. Absorption simulator apparatus endowed with an artificial membrane was purposely developed by experimental design. The apparent permeation coefficient (Papp) through excised porci...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.06.032
更新日期:2018-08-25 00:00:00
abstract::Pressure ulcers can form with excess pressure and shearing stress on skin tissue. Because pressure ulcer is often accompanies by exudates, selection of appropriate topical emulsion ointment is difficult. Blended ointments consisting of emulsion base and water-soluble base are clinically used for adjustment of wound mo...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.07.034
更新日期:2011-10-31 00:00:00
abstract::An aerosol system is described for the generation and delivery of measured doses of monodisperse therapeutic drug particles to the human lungs. The system comprises a spinning top aerosol generator (STAG), aerosol chamber and inhalation control unit. Monodisperse aerosols allow drug particle size effects to be studied...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(03)00032-2
更新日期:2003-03-26 00:00:00
abstract::An intermolecular complex formed from a 1:1 weight ratio of chitosan (CS, molecular weight 30 kDa) and sulfobutyl ether β-cyclodextrin (SBE-β-CyD, degree of substitution 7) was less soluble than either of the original components. The release of famotidine from tablets composed of a simple mixture of CS and SBE-β-CyD i...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.04.022
更新日期:2015-06-20 00:00:00
abstract::The systemic administration of methotrexate (MTX), a commonly used, antineoplastic drug which is also used in cutaneous disorders, is primarily associated with prolonged retention in the body and consequently with side effects. Innovative drug delivery techniques and alternative administration routes would therefore c...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.07.058
更新日期:2017-09-15 00:00:00
abstract::Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was asses...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.04.021
更新日期:2015-07-05 00:00:00
abstract::The aim of the present work was the development of a powder formulation for the delivery of manuka honey (MH) bioactive components in the treatment of chronic skin ulcers. In particular pectin (PEC)/chitosan glutamate (CS)/hyaluronic acid (HA) mini-capsules were obtained by inverse ionotropic gelation in presence of c...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.10.050
更新日期:2017-01-10 00:00:00
abstract:PURPOSE:This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits. METHODS:A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induc...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00482-8
更新日期:2000-08-25 00:00:00
abstract::The objective of this study was to evaluate the combination of pH-dependent and time-dependent polymers as a single coating for design of colon delivery system of indomethacin pellets. Eudragit S100 and Eudragit L100 were used as pH-dependent polymers and Eudragit RS was used as a time-dependent polymer. A statistical...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.05.011
更新日期:2006-08-31 00:00:00
abstract::The potential of two derivatives of vitamin E, i.e. α-tocopheryl phosphate (TP) and di-α-tocopheryl phosphate (T2P), for the protection and delivery of therapeutics is being investigated in our laboratory and some promising results have been obtained so far. Novel nanocarrier systems containing TP, T2P and different l...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.06.037
更新日期:2017-08-07 00:00:00