Anticancer drug screening is one of the most important research and development processes to develop new drugs for cancer treatment. However, there is a problem resulting in gaps between the in vitro ...drug screening and preclinical or clinical study. This is mainly because the condition of cancer cell culture is quite different from that in vivo. As a trial to mimic the in vivo cancer environment, there has been some research on a three-dimensional (3D) culture system by making use of biomaterials. The 3D culture technologies enable us to give cancer cells an in vitro environment close to the in vivo condition. Cancer cells modified to replicate the in vivo cancer environment will promote the biological research or drug discovery of cancers. This review introduces the in vitro research of 3D cell culture systems with biomaterials in addition to a brief summary of the cancer environment.
Purpose of the present research work was to evaluate the biological distribution of differently size gold nanoparticles (NP) up on intravenous administration in mice. Another objective was to study ...effect of particle size on biological distribution of gold NP to enable their diverse applications in nanotechnology.
Gold NP of different particle sizes, mainly 15, 50, 100 and 200
nm, were synthesized by modifying citrate ion concentration. Synthesized gold nanoparticles were characterized by SEM and their size distribution was studied by particle size analyzer. Gold NP was suspended in sodium alginate solution (0.5%, w/v) and administered to mice (1
g/kg, intravenously)
n
=
3. After 24
h of administration of gold NP, blood was collected under light ether anesthesia, mice were sacrificed by cervical dislocation and various tissues/organs were removed. The tissues were then washed with saline, homogenized and lysed with aqua regia. The determination of gold in samples was carried out quantitatively by inductively coupled plasma mass spectrometry (ICP-MS).
SEM study revealed spherical morphology of gold NP with narrow particle size distribution. Biodistribution study revealed gold NPs of all sizes were mainly accumulated in organs like liver, lung and spleen. The accumulation of gold NP in various tissues was found to be depending on particle size. 15
nm gold NP revealed higher amount of gold and number of particles in all the tissues including blood, liver, lung, spleen, kidney, brain, heart, stomach. Interestingly, 15 and 50
nm gold NP were able to pass blood–brain barrier as evident from gold concentration in brain. Two-hundred nanometers gold NP showed very minute presence in organs including blood, brain, stomach and pancreas.
The results revealed that tissue distribution of gold nanoparticles is size-dependent with the smallest 15
nm nanoparticles showing the most widespread organ distribution.
The objective of this study is to investigate the influence of shaking culture on the biological functions of cell aggregates incorporating gelatin hydrogel microspheres in terms of the ...microspheres/cells ratio. The mixture of MC3T3-E1 cells and the microspheres was cultured in the U-bottomed wells of 96-well plate pre-coated with poly (vinyl alcohol) (PVA) to form cell aggregates incorporating microspheres. When incubated in the static or shaking culture, the size of cell aggregates increased with amounts of gelatin hydrogel microspheres but was similar between the two cultures. At the smaller ratio of microspheres to cells, the viability of cell aggregates under the shaking culture was significantly higher than that of static culture. On the other hand, there was no significant difference in the viability between them at the higher ratio. Gelatin hydrogel microspheres enabled to enhance ATP and mitochondrial activities of cell aggregates under the shaking culture. The effect was high at the smaller microspheres/cells ratio. It is concluded that the shaking culture was promising to allow cells to enhance their activities.
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•Cyclosporin A-loaded 30-nm PLGA-PEG-PLGA nanoparticles were prepared.•The nanoparticles efficiently accumulated and permeated the drug in rat skin.•The nanoparticles were observed in ...the epidermis and dermis layer of rat skin.•The nanoparticles showed relatively high drug permeability in Strat-M®.
The aim of this study was to investigate the skin permeability of a hydrophobic drug when using poly(dl-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(dl-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) as a drug carrier. Two types of PLGA-PEG-PLGA nanoparticles with an average particle size of 30 nm and poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for comparison were prepared using a combination of an antisolvent diffusion method with preferential solvation. Cyclosporin A was used as a hydrophobic model drug. From the results of the in vitro release test, it was confirmed that the release of the drug from the nanoparticles was relatively fast in the PLGA-PEG-PLGA nanoparticles. This result suggested that, compared to PLGA nanoparticles, the thermodynamic activity of PLGA-PEG-PLGA nanoparticles increased and the diffusion of the drug into the stratum corneum was promoted. The results of studies on skin permeability using rat skin and a transdermal delivery route showed that PLGA-PEG-PLGA nanoparticles were useful for efficient drug skin permeation and can deliver the drugs deep into the epidermal and dermal layers. Additionally, in the membrane permeability tests using Strat-M®, which imitates human skin, the membrane permeation amount of the drug was significantly increased when PLGA-PEG-PLGA nanoparticles were used compared with when PLGA nanoparticles were used.
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•Donepezil hydrochloride-loaded PLGA nanoparticles were prepared.•Surface charge number density changed positively by coating with chitosan.•Chitosan-coated nanoparticles were ...suitable for iontophoresis.•Positively charged substance was delivered stratum corneum and deep hair follicles.
Recently, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles prepared using a combination of an antisolvent diffusion method with preferential solvation was shown to be beneficial for the iontophoretic transdermal delivery of therapeutic agents. Also, this preparation method can contain a hydrophilic drug. However, since PLGA nanoparticles were negatively charged, it was difficult to apply iontophoresis for positively charged hydrophilic drugs. In this study, we prepared positively charged PLGA nanoparticles containing donepezil hydrochloride (DP). DP was used as a positively charged hydrophilic drug model. The PLGA nanoparticles were coated with chitosan hydroxypropyltrimonium chloride. The average particle diameter of the nanoparticles was 117.7±60.6nm and the surface charge number density changed from negative to positive. Ex vivo skin accumulation study was carried out using abdominal rat skin and a Franz-type diffusion cell with/without iontophoresis. When iontophoresis was applied, the DP concentration in the rat skin of chitosan-coated PLGA nanoparticles was 2.2 times higher than that of non-coated PLGA nanoparticles. This indicated that chitosan-coated PLGA nanoparticles were suitable for iontophoresis. To investigate the transdermal delivery route of the nanoparticles, we prepared chitosan-coated PLGA nanoparticles containing DP, coumarin-6, and rhodamine 6G. Coumarin-6 and rhodamine 6G were used as a trace marker of the PLGA nanoparticles and positively charged hydrophilic drug model, respectively. From the results of ex vivo accumulation test of this fluorescent nanoparticles, it was suggested that positively charged hydrophilic drugs reached the hair follicles as a nanoparticle, and then they were released from the nanoparticles.
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•Hen egg-white lysozyme was contained in polymeric nanoparticles.•Iontophoresis and the nanoparticle carrier delivered antigen to hair follicles.•The immune response was stronger than ...that of subcutaneous injection.
Transdermal administration of poly(dl-lactide-co-glycolide) (PLGA) nanoparticles using iontophoresis (IP) is useful for efficient drug delivery to hair follicles. In this study, we investigated the possibility of using it in allergen immunotherapy. Hen egg-white lysozyme (HEL) was used as a model antigen. We successfully prepared PLGA nanoparticles with a mean volume diameter of 98.4 ± 36.8 nm using an antisolvent diffusion method. The PLGA nanoparticles were coated with chitosan hydroxypropyltrimonium chloride to shield the PLGA-derived negative charge. The surface charge number density was calculated to be 1.28 × 10−2 M, confirming that the particles had positive charges. An uptake test into dendritic cells was performed using fluorescently labeled HEL. The results of FACS measurement showed that the usage of the nanoparticle carrier increased the mean fluorescence intensity by 5.6 times. An ex vivo skin accumulation study was carried out using abdominal mouse skin and a Franz-type diffusion cell with and without IP. When IP was applied to the nanoparticles, the HEL concentration in mouse skin was 9.6 times higher than that without IP and 2.1 times higher than that of the HEL solution. Images of skin sections confirmed that HEL was efficiently delivered to hair follicles using IP and nanoparticle carriers. HEL-specific IgG1 and IgG2a titers were determined in an in vivo percutaneous immunoreactivity study. Ten weeks after the initiation of the test using IP and the nanoparticle carrier, HEL-specific IgG1 and IgG2a titers were 7.4 × 104 and 6.6 × 102, respectively. Both values were higher than those obtained by subcutaneous injection of HEL solution, indicating the effectiveness of the combined use of IP and nanoparticle carriers.
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•Paclitaxel-encapsulated micelles were prepared using a phosphoester compound.•The micelles showed faster drug release at pH 5.0, compared to pH 7.4.•Hemolytic effects and ...cytotoxicity of the micelles were investigated.•The micelles efficiently delivered paclitaxel to the tumor in vivo.
Phosphoester compounds are promising materials with expected biocompatibility; however, little has been reported on the use of phosphoester compounds for micelle formulations. In this study, paclitaxel (PTX)–encapsulated micelles were prepared using four kinds of alkyl di(MePEG-lactate) phosphates. From the results of the determination of critical micelle concentrations and an in vitro stability test, it was shown that a compound to which 1-eicosanol was introduced as a side chain was desirable in the preparation of PTX-encapsulated micelles (PTX-micelles). The mean volume diameter and PTX content of the micelles were 135.7 ± 52.2 nm and 3.9% ± 0.2%, respectively. in vitro release tests of the micelles were performed at different pH levels. Twenty-four hours after the start of the release test, the cumulative PTX release rate of PTX-micelles at pH 5.0 reached 96.2%, which was three times higher than that at pH 7.4. As a result of the degradation test of the compound used for the micelle, it was confirmed that this compound degraded faster at pH 5.0 than at pH 7.4. The hemolysis rate of drug-free micelles was 0.8%–1.4%, and the biocompatibility of this micelle as a drug carrier was suggested. In addition, the effectiveness of PTX-micelles in cancer treatment was evaluated via biodistribution study. PTX concentration in the tumor was significantly increased in the group administered PTX-micelles as compared with the group administered PTX solution. These results suggest that phosphoester compounds are useful in preparing biocompatible pH-responsive carriers.
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•The usability of poly(lactide-co-glycolide) as a drug carrier for BNCT was studied.•Biodistributions of PLGA and PLLGA nanoparticles were observed.•100-nm PLLGA nanoparticles reached ...113.9±15.8μg B/g of tumor tissue at 8h.•Intratumoral boron concentration was increased by nanoparticulation.
Poly(DL-lactide-co-glycolide) (PLGA) has been widely used and studied because of its biocompatibility and biodegradability. Recently, the usefulness of nanoparticles using poly(L-lactide-co-glycolide) (PLLGA) having a higher glass transition temperature than PLGA was suggested. In this study, we investigated the availability of boron compound-loaded PLGA and PLLGA nanoparticles for boron neutron capture therapy (BNCT) by conducting biodistribution study using tumor-bearing mice. o-Carborane, a hydrophobic boron compound, was used as a boron carrier, and o-carborane-albumin conjugate was used as a control. We prepared PLGA and PLLGA nanoparticles with diameters of 100nm and 150nm. In 100-nm PLLGA nanoparticles, the boron concentration in the tumor reached 113.9±15.8μg/g of tissue at 8h after administration. This result indicated that 100-nm PLLGA nanoparticles were able to achieve an intratumoral 10B concentration of 20μg/g without replacing the 11B with 10B. In addition, by nanoparticulation using PLGA7510 and PLLGA7510, intratumoral boron concentration was 1.7–3.2 and 3.5–4.2 times higher than that of the o-carborane-albumin conjugate, respectively. The tumor/blood ratios of boron concentration reached over 5 at 8–12h after injection. Boron atoms in nanoparticles were excreted mainly in the urine, and characteristic accumulation was not observed in other organs. These results suggested that 100-nm PLLGA nanoparticles were particularly useful for BNCT.
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•Poly(lactide-co-glycolide) of lactic acid/glycolic acid=9/1 was synthesized.•Glass transition temperature (Tg) of copolymers affected drug release behavior.•Tg of ...poly(l-lactide-co-glycolide) was higher than poly(dl-lactide-co-glycolide).•Poly(l-lactide-co-glycolide) prevented the initial drug burst from nanoparticles.
Poly(lactide-co-glycolide) has been widely used and studied because of its biocompatibility and biodegradability. Many drug-loaded particles have been developed using this copolymer, however, information on its release behavior is lacking, especially for nanoparticles prepared using poly(l-lactide-co-glycolide). In this study, we used poly(dl-lactide-co-glycolide) (PLGA) and poly(l-lactide-co-glycolide) (PLLGA) with a 75/25 and 90/10 monomer composition of lactic acid/glycolic acid and molecular weights of 10,000. We determined the crystalline states, glass transition temperatures, and activation energies of the copolymers. Rifampicin-loaded PLGA7510, PLLGA7510, PLGA9010, or PLLGA9010 nanoparticles with 100-, 200- and 400-nm diameters were prepared, and in vitro release tests were carried out in phosphate-buffered saline at 37°C or 25°C for a week. The cumulative release ratio of rifampicin from nanoparticles using poly(l-lactide-co-glycolide) as a drug carrier was significantly lower than the release ratio from nanoparticles using poly(dl-lactide-co-glycolide), since the glass transition temperature of poly(l-lactide-co-glycolide) was 7°C higher than that of poly(dl-lactide-co-glycolide) at the same monomer composition. In addition, we found that the glass transition temperatures of the copolymers exerted a considerable influence on the initial release burst from the drug-loaded nanoparticles.
The usefulness of poly(lactide-co-glycolide) nanoparticles as a boron compound carrier for boron neutron capture therapy has been recently reported. In this study, chitosan-modified ...poly(DL-lactide-co-glycolide) (PLGA) nanoparticles were prepared to better facilitate the delivery of boron to the tumor. Chitosan hydroxypropyltrimonium chloride (CS), which can easily be modified for compatibility with PLGA nanoparticles, was used as chitosan. o-Carborane-loaded PLGA nanoparticles (bare nanoparticles) with a mean volume diameter of 111.4 ± 30.1 nm, and o-Carborane-loaded PLGA nanoparticles coated with CS (CS-coated nanoparticles) with a mean volume diameter of 113.6 ± 32.5 nm were prepared via an emulsion solvent evaporation method. Electrophoretic mobility was measured to calculate the particle surface charge number density of these particles; particle surface charge number densities of -1.91 mM and 20.8 mM were obtained for the bare and CS-coated nanoparticles, respectively. This result indicates that the particle surface was fully covered with CS. In vitro cellular uptake tests were carried out by using B16 melanoma cells. From the results of observation via confocal laser scanning microscopy, it was revealed that CS-coated nanoparticles existed around the cell nucleus, and were localized in the cytoplasm. Cellular uptakes of bare and CS-coated nanoparticles were quantitatively assessed by using fluorescence-activated cell sorting; the mean fluorescence intensity of CS-coated nanoparticles was three times higher than that of bare nanoparticles. The number of boron atoms in B16 melanoma cells was also investigated. Inductively coupled plasma atomic emission spectroscopy revealed that the number of boron atoms per cell of CS-coated nanoparticles was 1.8 times higher than that of bare nanoparticles. Based on these findings, we consider CS-coated nanoparticles to be suitable for boron neutron capture therapy.
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