• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.517-535
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• 2014

Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained-release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.

• Molecules and Cells
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• v.42 no.11
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• pp.755-762
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• 2019

Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.49-54
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• 2014

Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materials and Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles ($Fe_3O_4$) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA-VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at $37^{\circ}C$. Magnetic iron oxide nanoparticles ($Fe_3O_4$) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at $40^{\circ}C$ and in acidic pH compared to that $37^{\circ}C$ and basic pH. Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.56-56
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• 2003

Carduus marianus extract (formally called silymarin) have been used mainly as a medicament for hepatobiliary diseases. The major component of silymarin is silybin, which constitutes between 50 and 70% of the drug and is the major active component. Many experiments show the efficacy of silybin parenterally administerated. But, its bioavailability is low after oral administration due to its low solubility in water. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.296.2-296.2
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• 2003

Carduus marianus extract (formally called silymarin) have been used mainly as a medicament for hepatobiliary diseases. The major component of silymarin is silybin, which constitutes between 50 and 70％ of the drug and is the major active component. Many experiments show the efficacy of silybin parenterally administerated. But, its bioavalability is low after oral administration due to its low solubility in water. (omitted)

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.155-165
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• 1994

Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing $300{\sim}350\;g$. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants, $K_s$ and $K_r$ respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.

• Polymer(Korea)
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• v.29 no.3
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• pp.288-293
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• 2005

Osmotic granule system which is one of the drug delivery systems has been developed to improve manufacturing process and other problems of tablet osmotic systems. It consists of water swellable seed layer, nifedipine drug layer, and drug release controlled membrane layer and manufactured by fluidized bed coater. The granule size and mombrane thickness can be controlled by various amounts of seed and coating solution, respectively. It could be observed that the morphology of osmotic granule was different at each coating step as well as type of coating solution. The bigger the size of granule, the slower the release rate was observed due to decreasing the total specific surface wed of granule. Also, it was observed that the increase of membrane thickness was caused to retard the dissolution of nifedipine due to decreasing the water absorption rate. The drug solubility for dissolution media is greatly affected to nifedipine release. From these results, we assured that osmotic granule can be fabricated by fluidized bed coating methods, and the appropriate release profile could be controlled by the controlling of bead size, membrane thickness and dissolution media.

• The Korean Journal of Pain
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• v.5 no.1
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• pp.23-28
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• 1992

The use of epidural narcotics to treat cancer pain was first described by Behar et al in 1979. More recently, a variety of implantable INDSs have been described for long-term intraspinal narcotic administration. Especially, among these systems INDS typeIII which is designed by Poletti et al is relatively low cost and less risk of infection, therefore this system has been widely accepted but the clinical experience is insufficient yet. 1, Problems, 1) thorough education of patients and care-givers about this system the method of drug delivery and the situations could be happen in using this system. 2) high cost of continuous drug delivery system 3) legal problems about morphine carry-out in the case of bolus infusion by syringe 1. Complications; 1) by morphine; Significant respiratory depression was not found in all 21cases. other morphine-related complications were occurred occasionally but improved within a few days by appropriate treatment. 2) by system, Blockage or leakage of catheter was occurred in 2cases and wound infection was occurred in 2cases and so reimplantation was done.

• Ceramist
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• v.22 no.3
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• pp.269-280
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• 2019

Ceramic layered double hydroxide (LDH) nanohybrids have attracted considerable interest in biomedical science due to their unique structural feature and characteristics in biological condition. Many studies on LDH nanoparticles have been reported in diagnosis applications including magnetic resonance imaging (MRI) contrast agents in order to not only provide better imaging performance through multimodal imaging strategy, but realize therapeutic function which treat cancers in one platform. This review highlights the recent progress in MRI T₁ contrast agent, dual modal imaging system, and MRI-guided drug delivery systems ranging from synthetic method and characterization to evaluation in vitro and in vivo based on the ceramic LDH nanohybrids. Future research directions are also suggested for next-generation bio-imaging contrast agent.

• Biomaterials and Biomechanics in Bioengineering
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• v.2 no.3
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• pp.159-172
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• 2015

Treatment of polymicrobial infected musculoskeletal defects continues to be a challenge in orthopaedics. This research investigated single and dual-delivery of two antibiotics, vancomycin and amikacin, targeting different classes of microorganism from a biodegradable calcium sulfate-chitosan-nHA microsphere composite scaffold. The addition of chitosan-nHA was included to provide additional structure for cellular attachment and as a secondary drug-loading device. All scaffolds exhibited an initial burst of antibiotics, but groups containing chitosan reduced the burst for amikacin at 1hr by 50%, and vancomycin by 14-25% over the first 2 days. Extended elution was present in groups containing chitosan; amikacin was above MIC ($2-4{\mu}g/mL$, Pseudomonas aeruginosa) for 7-42 days and vancomycin was above MIC ($0.5-1{\mu}g/mL$ Staphylococcus aureus) for 42 days. The antibiotic activity of the eluates was tested against S. aureus and P. aeruginosa. The elution from the dual-loaded scaffold was most effective against S. aureus (bacteriostatic 34 days and bactericidal 27 days), compared to vancomycin-loaded scaffolds (bacteriostatic and bactericidal 14 days). The dual- and amikacin-loaded scaffolds were effective against P. aeruginosa, but eluates exhibited very short antibacterial properties; only 24 hours bacteriostatic and 1-5 hours bactericidal activity. For all groups, vancomycin recovery was near 100% whereas the amikacin recovery was 41%. In conclusion, in the presence of chitosan-nHA microspheres, the dual-antibiotic loaded scaffold was able to sustain an extended vancomycin elution longer than individually loaded scaffolds. The composite scaffold shows promise as a dual-drug delivery system for infected orthopaedic wounds and overcomes some deficits of other dual-delivery systems by extending the antibiotic release.