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1.
Darshana S Jain Rajani B Athawale Amrita N Bajaj Shruti S Shrikhande Peeyush N Goel Yuvraj Nikam Rajiv P Gude 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1):18
Background
Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.Results
PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.Conclusion
PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity. 相似文献2.
Purpose
Preparation, optimization and in vitro evaluation of core-shell nanoparticles comprising of a hydrophilic core of BSA surrounded by a hydrophobic shell of PLGA for loading water-soluble drugs.Methods
A double emulsion method was optimized for preparation of BSA-PLGA based core-shell nanoparticles. Proof of concept for core-shell type structure was established by visual techniques like confocal microscopy and TEM. Characterization was done for particle size, encapsulation efficiency, drug loading and in vitro drug release. Cellular uptake was assessed using confocal microscopy, bio-TEM and HPLC assay, and cytotoxic activity was tested by MTT assay in MG-63 osteosarcoma cells.Results
The optimized core-shell nanoparticles showed a particle size of 243 nm (PDI-0.13) and encapsulation efficiency of 40.5% with a drug loading of 8.5% w/w. In vitro drug release studies showed a sustained release for 12 h. Cellular uptake studies indicated a rapid and efficient uptake within 2 h. TEM studies indicated that the core-shell nanoparticles were localized in cytoplasm region of the cells. Gemcitabine loaded core-shell nanoparticles showed enhanced cytotoxicity against MG-63 cells as compared to marketed formulation of gemcitabine (GEMCITE®).Conclusion
These results indicate that core-shell nanoparticles can be a good carrier system for delivering hydrophilic drugs like gemcitabine successfully to the cells with enhanced efficacy.Core-Shell Nanoparticles with a hydrophilic BSA core and hydrophobic PLGA shell for carrier system of hydrophilic drugs 相似文献
3.
Ghobad Mohammadi Amineh Shakeri Ali Fattahi Pardis Mohammadi Ali Mikaeili Alireza Aliabadi Khosro Adibkia 《Pharmaceutical research》2017,34(2):301-309
Purpose
Nystatin loaded PLGA and PLGA-Glucosamine nanoparticles were formulated. PLGA were functionalized with Glucosamine (PLGA-GlcN) to enhance the adhesion of nanoparticles to Candida Albicans (C.albicans) cell walls.Method
Quasi-emulsion solvent diffusion method was employed using PLGA and PLGA-GlcN with various drug–polymer ratios for the preparation of nanoparticles. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency and release properties. DSC, SEM, XRPD, 1H-NMR, and FT-IR were performed to analyze the physicochemical properties of the nanoparticles. Antifungal activity of the nanoparticles was evaluated by determination of MICs against C.albicans.Results
The spectra of 1H-NMR and FT-IR analysis ensured GlcN functionalization on PLGA nanoparticles. SEM characterization confirmed that particles were in the nanosize range and the particle size for PLGA and PLGA-GlcN nanoparticles were in the range of 108.63?±?4.5 to 168.8?±?5.65 nm and 208.76?±?16.85 nm, respectively. DSC and XRPD analysis ensured reduction of the drug crystallinity in the nanoparticles. PLGA-GlcN nanoparticles exhibit higher antifungal activity than PLGA nanoparticles.Conclusion
PLGA-GlcN nanoparticles showed more antifungal activity with appropriate physicochemical properties than pure Nystatin and PLGA nanoparticles.4.
Chirasak Kusonwiriyawong Vimolmas Lipipun Nontima Vardhanabhuti Qiang Zhang Garnpimol C. Ritthidej 《Pharmaceutical research》2013,30(6):1677-1697
Purpose
Spray-dried chitosan microparticles for cellular delivery of antigen to dendritic cells (DC) and macrophages (M?) were investigated.Methods
Chitosan microparticles were prepared by spray drying. For comparison, poly(lactic-co-glycolic acid) (PLGA) and poly(α-butyl cyanoacrylate) (BCA) micro-/nanoparticles were generated. Bovine serum albumin (BSA) was used as a model antigen. The particles were characterized in terms of size, morphology, surface charge, surface composition, protein content, entrapment efficiency, in vitro release, and protein integrity. Additionally, they were subject to cell viability and cellular uptake study with DC and M?.Results
Size of chitosan, PLGA, and BCA micro-/nanoparticles ranged between 3.11–7.18, 0.94–6.26, and 0.30–6.34 μm, respectively. Particle morphology and in vitro protein release varied, depending on polymer type, particle composition and preparation process parameters. Chitosan microparticles were cationic, while PLGA microparticles were neutral. BCA micro-/nanoparticles were either anionic or cationic, according to polymerization pH. Protein content and entrapment efficiency of chitosan and PLGA microparticles were relatively consistent. Only integrity and conformational structure of protein encapsulated in chitosan microparticles were completely retained. Chitosan and PLGA microparticles were non-toxic to DC and M?, but the former were internalized more efficiently.Conclusions
Spray-dried chitosan microparticles delivered the antigen efficiently to DC and M?. 相似文献5.
M. F. Ebbesen B. Whitehead B. Ballarin-Gonzalez P. Kingshott K. A. Howard 《Pharmaceutical research》2013,30(7):1758-1767
Purpose
This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic “nano-shields” and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein and cellular interactions.Methods
Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared with a hydrophilic PEGylated “nano-shield” inserted at different levels by hydrophobic anchoring using either a phospholipid-PEG conjugate or the copolymer PLGA-block-PEG by an emulsification/diffusion method. Surface and bulk analysis was performed including X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) and zeta potential. Cellular uptake was investigated in RAW 264.7 macrophages by flow cytometry.Results
Sub-micron nanoparticles were formed and the combination of (NMR) and XPS revealed increasing PEG levels at the particle surface at higher PLGA-b-PEG copolymer levels. Reduced cellular interaction with RAW 264.7 cells was demonstrated that correlated with greater surface presentation of PEG.Conclusion
This work demonstrates a versatile procedure for decorating nanoparticle surfaces with hydrophilic “nano-shields”. XPS in combination with NMR enabled precise determination of PEG at the outmost surface to predict and optimize the biological performance of nanoparticle-based drug delivery. 相似文献6.
Purpose
To create poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), where a drug-encapsulating NP core is covered with polyethylene glycol (PEG) in a normal condition but exposes a cell-interactive TAT-modified surface in an environment rich in matrix metalloproteinases (MMPs).Methods
PLGA NPs were modified with TAT peptide (PLGA-pDA-TAT NPs) or dual-modified with TAT peptide and a conjugate of PEG and MMP-substrate peptide (peritumorally activatable NPs, PANPs) via dopamine polymerization. Cellular uptake of fluorescently labeled NPs was observed with or without a pre-treatment of MMP-2 by confocal microscopy and flow cytometry. NPs loaded with paclitaxel (PTX) were tested against SKOV-3 ovarian cancer cells to evaluate the contribution of surface modification to cellular delivery of PTX.Results
While the size and morphology did not significantly change due to the modification, NPs modified with dopamine polymerization were recognized by their dark color. TAT-containing NPs (PLGA-pDA-TAT NPs and PANPs) showed changes in surface charge, indicative of effective conjugation of TAT peptide on the surface. PLGA-pDA-TAT NPs and MMP-2-pre-treated PANPs showed relatively good cellular uptake compared to PLGA NPs, MMP-2-non-treated PANPs, and NPs with non-cleavable PEG. After 3 h treatment with cells, PTX loaded in cell-interactive NPs showed greater toxicity than non-interactive ones as the former could enter cells during the incubation period. However, due to the initial burst drug release, the difference was not as clear as microscopic observation.Conclusions
PEGylated polymeric NPs that could expose cell-interactive surface in response to MMP-2 were successfully created by dual modification of PLGA NPs using dopamine polymerization. 相似文献7.
Mohammed M. Ibrahim Abd-Elgawad H. Abd-Elgawad Osama A. Soliman Monica M. Jablonski 《Pharmaceutical research》2013,30(11):2818-2831
Purpose
Preparation of topical ophthalmic formulations containing brimonidine-loaded nanoparticles prepared from various biodegradable polymers—PCL, PLA and PLGA—for sustained release of brimonidine as a once daily regimen for management of glaucoma.Methods
Nanoparticles were prepared using spontaneous emulsification solvent diffusion method then characterized regarding their particle size, zeta potential, morphology and drug contents. Brimonidine-loaded nanoparticles were incorporated into eye drops, temperature-triggered in situ gelling system and preformed gel and characterized regarding their pH, viscosity, uniformity of drug contents, in vitro release study, in vitro cytotoxicity and in vivo intraocular pressure (IOP) lowering effects.Results
The results of optimized brimonidine-loaded PCL-, PLGA- and PLA-NPs respectively, are: particle sizes of 117.33?±?4.58 nm, 125.67?±?5.15 nm and 131.67?±?3.79 nm; zeta potentials of ?18.5?±?2.87 mV, ?21.82?±?2.7 mV and ?28.11?±?2.21 mV; and encapsulation efficiencies of 77.97?±?1.38%, 68.65?±?3.35% and 73.52?±?2.92%. TEM analyses revealed that all NPs have spherical shapes with dense core and distinct coat. In vitro release data showed a sustained release without any burst effect with Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are non-toxic. Also all formulations possessed a sustained IOP lowering effect compared to Alphagan® P eye drops.Conclusions
Our formulations showed prolonged management of glaucoma that should meet with better patient compliance as a once-daily formulation. 相似文献8.
Purpose
The aim of this work was to evaluate in vivo poly(lactide)-d-α-tocopheryl polyethylene glycol 1,000 succinate nanoparticles (PLA–TPGS NPs) for controlled and sustained small molecule drug chemotherapy.Methods
The drug-loaded PLA–TPGS NPs were prepared by the dialysis method. Particle size, surface morphology and surface chemistry, in vitro drug release and cellular uptake of NPs were characterized. In vitro and in vivo therapeutic effects of the nanoparticle formulation were evaluated in comparison with Taxol®.Results
The PLA–TPGS NP formulation exhibited significant advantages in in vivo pharmacokinetics and xenograft tumor model versus the PLGA NP formulation and the pristine drug. Compared with Taxol®, the PLA–TPGS NP formulation achieved 27.4-fold longer half-life in circulation, 1.6-fold larger area-under-the-curve (AUC) with no portion located above the maximum tolerance concentration level. For the first time in the literature, one shot for 240 h chemotherapy was achieved in comparison with only 22 h chemotherapy for Taxol® at the same 10 mg/kg paclitaxel dose. Xenograft tumor model further confirmed the advantages of the NP formulation versus Taxol®.Conclusions
The PLA–TPGS NP formulation can realize a way of controlled and sustained drug release for more than 10 days, which relieves one of the two major concerns on cancer nanotechnology, i.e. feasibility. 相似文献9.
Wanyi Tai Zhijin Chen Ashutosh Barve Zhonghua Peng Kun Cheng 《Pharmaceutical research》2014,31(3):706-719
Purpose
Rapamycin has demonstrated potent anti-tumor activity in preclinical and clinical studies. However, the clinical development of its formulations was hampered due to its poor solubility and undesirable distribution in vivo. Chemical modification of rapamycin presents an opportunity for overcoming the obstacles and improving its therapeutic index. The objective of this study is to develop a drug-polymer conjugate to increase the solubility and cellular uptake of rapamycin.Methods
We developed the rapamycin-polymer conjugate using a novel, linear, poly(ethylene glycol) (PEG) based multiblock copolymer. Cytotoxicity and cellular uptake of the rapamycin-polymer conjugate were evaluated in various cancer cells.Results
The rapamycin-polymer conjugate provides enhanced solubility in water compared with free rapamycin and shows profound activity against a panel of human cancer cell lines. The rapamycin-polymer conjugate also presents high drug loading capacity (wt% ~ 26%) when GlyGlyGly is used as a linker. Cellular uptake of the conjugate was confirmed by confocal microscopic examination of PC-3 cells that were cultured in the presence of FITC-labled polymer (FITC-polymer).Conclusion
This study suggests that the rapamycin-polymer conjugate is a novel anti-cancer agent that may provide an attractive strategy for treatment of a wide variety of tumors. 相似文献10.
Purpose
Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly (lactic-coglycolicacid) (PLGA).Methods
BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor).Results
FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 min. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 h.Conclusions
The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs. 相似文献11.
Matshawandile Tukulula Luis Gouveia Paulo Paixao Rose Hayeshi Brendon Naicker Admire Dube 《Pharmaceutical research》2018,35(6):111
Purpose
Mycobacterium tuberculosis which causes tuberculosis, is primarily resident within macrophages. 1,3-β-glucan has been proposed as a ligand to target drug loaded nanoparticles (NPs) to macrophages. In this study we characterized the intracellular pharmacokinetics of the anti-tubercular drug rifampicin delivered by 1,3-β-glucan functionalized PLGA NPs (Glu-PLGA). We hypothesized that Glu-PLGA NPs would be taken up at a faster rate than PLGA NPs, and consequently deliver higher amounts of rifampicin into the macrophages.Methods
Carbodiimide chemistry was employed to conjugate 1,3-β-glucan and rhodamine to PLGA. Rifampicin loaded PLGA and Glu-PLGA NPs as well as rhodamine functionalized PLGA and Glu-PLGA NPs were synthesized using an emulsion solvent evaporation technique. Intracellular pharmacokinetics of rifampicin and NPs were evaluated in THP-1 derived macrophages. A pharmacokinetic model was developed to describe uptake, and modelling was performed using ADAPT 5 software.Results
The NPs increased the rate of uptake of rifampicin by a factor of 17 and 62 in case of PLGA and Glu-PLGA, respectively. Expulsion of NPs from the macrophages was also observed, which was 3 fold greater for Glu-PLGA NPs than for PLGA NPs. However, the ratio of uptake to expulsion was similar for both NPs. After 24 h, the amount of rifampicin delivered by the PLGA and Glu-PLGA NPs was similar. The NPs resulted in at least a 10-fold increase in the uptake of rifampicin.Conclusions
Functionalization of PLGA NPs with 1,3-β-glucan resulted in faster uptake of rifampicin into macrophages. These NPs may be useful to achieve rapid intracellular eradication of Mycobacterium tuberculosis.12.
Feng Wan Adam Bohr Morten Jonas Maltesen Simon Bjerregaard Camilla Foged Jukka Rantanen Mingshi Yang 《Pharmaceutical research》2013,30(4):1065-1076
Purpose
It is imperative to understand the particle formation mechanisms when designing advanced nano/microparticulate drug delivery systems. We investigated how the solvent power and volatility influence the texture and surface chemistry of celecoxib-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles prepared by spray-drying.Methods
Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties and drug release profile. The evaporation profiles of the feed solutions were investigated using thermogravimetric analysis (TGA).Results
Spherical PLGA microparticles were obtained, irrespectively of the solvent composition. The particle size and surface chemistry were highly dependent on the solvent power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures.Conclusions
The particle formation process is mainly governed by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition.13.
Purpose
Determine the efficiency of cationic nanoparticles prepared by blending poly (lactide-co-glycolide; PLGA) and methacrylate copolymer (Eudragit® E100) to deliver a therapeutic gene encoding mouse interleukin-10, in vitro and in vivo.Methods
Nanoparticles prepared with PLGA and E100 were evaluated for delivery of plasmid DNA encoding mouse interleukin-10 in vitro and in vivo in mice upon intramuscular injection. Blood-glucose, serum interferon-gamma levels and histology of pancreas were studied to determine therapeutic efficacy. Histological evaluation of skeletal muscle from the injection site was performed to assess the biocompatibility of nanoparticles.Results
PLGA/E100 nanoparticles showed endosomal escape evidenced by confocal microscopy and buffering ability. Transfecting HEK293 cells with plasmid-loaded PLGA/E100 nanoparticles resulted in significantly (p?0.05) greater expression of interleukin-10 compared to PLGA nanoparticles. Mice treated with PLGA/E100 nanoparticles displayed higher serum levels of interleukin-10 and lower blood glucose levels compared to those treated with interleukin-10 plasmid alone or PLGA nanoparticles. High expression of interleukin-10 facilitated suppression of interferon-gamma levels and reduced islet infiltration. Histology of muscle showed that nanoparticles were biocompatible and did not cause chronic inflammatory response.Conclusions
Nanoparticles prepared by blending PLGA with methacrylate can efficiently and safely deliver plasmid DNA encoding mouse interleukin-10 leading to prevention of autoimmune diabetes. 相似文献14.
Purpose
To propose a novel composite nanoemulsion formulation that contains no surfactant, but offers great stability and improved oral absorption capabilities.Methods
The nanoemulsions were prepared by dispersing the oil phase into aqueous solutions containing different amounts of the PMMA/silica composite nanoparticles. The stability was tested under extreme conditions. The structure features of the nanoemulsion droplets were investigated using Electron microscope. The in vitro drug release and in vivo drug absorption profiles after oral administration were investigated using Cyclosporin A as a model drug.Results
The composite nanoemulsion demonstrated great stability under various disruptive conditions. Electron microscopy studies indicated the existence of internal and surface domains in the nano-droplet structure. In vitro drug release and in vivo uptake characterizations also confirmed the unique interfacial properties of such nanoemulsion structures.Conclusions
The novel nanoemulsion formulation may have modulated drug release profiles and alternative oral absorption mechanisms, which could offer significant advantages compared to traditional emulsion formulations. 相似文献15.
Purpose
We evaluated the controlled release of lysozyme from various poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50-polyethylene glycol (PEG) block copolymers relative to PLGA 50/50.Methods
Lysozyme was encapsulated in cylindrical implants (0.8 mm diameter) by a solvent extrusion method. Release studies were conducted in phosphate buffered saline +0.02% Tween 80 (PBST) at 37°C. Lysozyme activity was measured by a fluorescence-based assay. Implant erosion was evaluated by kinetics of polymer molecular weight decline, water uptake, and mass loss.Results
Lysozyme release from an AB15 di-block copolymer (15% 5 kDa PEG, PLGA 28 kDa) was very fast, whereas an AB10 di-block copolymer (with 10% 5 kDa PEG, PLGA 45 kDa) and ABA10 tri-block copolymer (with 10% 6 kDa PEG, PLGA 27 kDa) showed release profiles similar to PLGA. We achieved continuous lysozyme release for up to 4 weeks from AB10 and ABA10 by lysozyme co-encapsulation with the pore-forming and acid-neutralizing MgCO3, and from AB15 by co-encapsulation of MgCO3 and blending AB15 with PLGA. Lysozyme activity was mostly recovered during 4 weeks.Conclusions
These block co-polymers may have utility either alone or as PLGA blends for the controlled release of proteins. 相似文献16.
Yingjia Li Ge Wen Dongxiao Wang Xia Zhang Yaoyong Lu Jianguo Wang Lijuan Zhong Hongbing Cai Xingmei Zhang Ying Wang 《Pharmaceutical research》2014,31(8):2054-2064
Purpose
The complementary strategy by combining targeting ligand-mediated selectivity and CPP-mediated transmembrane function could be exploit synergies for enhancing cellular uptake of nanoparticles with negative charge. A heparin-based nanoparticles with negative charge was fabricated by complementary strategy, which was expected to attain efficient uptake and simultaneously exert great anticancer activity.Methods
We synthesized heparin-based nanoparticles with targeting ligand folate and CPP ligand Tat to deliver paclitaxel (H-F-Tat-P NPs). The NPs were characterized by 1H NMR, DLS and TEM, respectively. The effect of dual ligands on system behavior in aqueous solution was investigated. Moreover, its cellular internalization and anticancer activity were detected by flow cytometry, confocal microscopy and MTT.Results
Folate played a key role in the formation of heparin-based NPs dependent on the balance of amphiphilic Tat and hydrophobic folate. Although H-F-Tat-P NPs primarily entered FR specific and non-specific cells by similar routes, there were no comparability due to cell-type specific variation. Unlike non-specific cells, the complementary ligands could help negative-charged NPs to enhance cellular uptake facilitating its endosome escape in specific cells thereby exhibiting great anticancer activity.Conclusions
The complementary strategy for negative-charged NPs was presented a promising delivery system for diverse anticancer agents enable simultaneously targeting and drug delivery. 相似文献17.
Jingwei Li Chi Zhang Jing Li Li Fan Xinguo Jiang Jun Chen Zhiqing Pang Qizhi Zhang 《Pharmaceutical research》2013,30(7):1813-1823
Purpose
A phage-displayed peptide TGN was used as a targeting motif to help the delivery of NAP-loaded nanoparticles across the blood–brain barrier (BBB), which sets an obstacle for brain delivery of NAP in vivo.Methods
Intracerebroventricular injection of Aβ1-40 into mice was used to construct in vivo model of Alzheimer’s disease. The water maze task was performed to evaluate the effects of the NAP formulations on learning and memory deficits in mice. The neuroprotective effect was tested by detecting acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity and conducting histological assays.Results
Intravenous administration of NAP-loaded TGN modified nanoparticles (TGN-NP/NAP) has shown better improvement in spatial learning than NAP solution and NAP-loaded nanoparticles in Morris water maze experiment. The crossing number of the mice with memory deficits recovered after treatment with TGN-NP/NAP in a dose dependent manner. Similar results were also observed in AChE and ChAT activity. No morphological damage and no detectable Aβ plaques were found in mice hippocampus and cortex treated with TGN-NP/NAP.Conclusions
TGN modified nanoparticles could be a promising drug delivery system for peptide and protein drug such as NAP to enter the brain and play the therapeutic role. 相似文献18.
Microspheres Prepared with PLGA Blends for Delivery of Dexamethasone for Implantable Medical Devices
Purpose
To develop and characterize microspheres using poly (lactic-co-glycolic acid) (PLGA) blends (PLGA5050 (25 KD) and PLGA6535 (70 KD)) for dexamethasone delivery to prevent foreign body response to implantable biosensors.Methods
A single emulsion based oil/water solvent evaporation/extraction method was used to prepare microspheres.Results
All the microspheres prepared exhibited the typical triphasic release profile, but with different initial burst release, lag phase and zero order release rates. The burst release was reduced when the two PLGA were mixed at a molecular level, whereas increase in burst release was observed when phase separation occurred. Microspheres prepared using PLGA blends had significantly shorter lag phase. The activation energy (Ea) of dexamethasone release from microspheres was similar to the Ea value of PLGA degradation. The release kinetics were significantly enhanced under accelerated conditions (45 and 53°C) without altering the release mechanism of the post-burst phase. A rank order correlation between accelerated and “real-time” release kinetics was observed.Conclusions
Polymer blends of PLGA can produce microspheres with reduced lag time. The accelerated release testing conditions investigated can discriminate the formulations and predict “real-time” release. Such accelerated release testing can be used as a rapid screening method to facilitate formulation development. 相似文献19.
Zhiwen Zhang Shijun Jiang Zeying Liu Baohua Niu Wangwen Gu Yaping Li Jingbin Cui 《Pharmaceutical research》2014,31(9):2266-2275
Purpose
We are reporting on the development of a unique drug delivery platform by directed self-assembly technique to improve the oral delivery of hydrophobic drugs.Methods
Herein, a series of probucol directed self-assembled nanoparticles (PDN) were developed with two components of probucol and surfactant such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP-PDN and HS-PDN. The formation of various PDNs was determined by in vitro characterization and the physicochemical properties of these PDNs were determined. Moreover, the performance of PDN in enhancing the oral delivery and possible correlation between the in vitro properties and in vivo performances were investigated.Results
PDN was homogenous nanometer-sized particles with negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In particular, the oral bioavailability of these PDN was significantly improved 3.0, 4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced cellular uptake and oral bioavailability were correlated with the characters of involved surfactants and the particle size of PDN.Conclusions
Thereby, the directed self-assembled nanoparticles could provide a new strategy for enhancing the oral delivery of hydrophobic drugs. 相似文献20.
das Neves J Michiels J Ariën KK Vanham G Amiji M Bahia MF Sarmento B 《Pharmaceutical research》2012,29(6):1468-1484