• 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.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.137-144
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• 2007

Although lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase, has been shown to have anti-cancer actions, the effect on human hepatoma cells was not investigated. Moreover, the exact mechanism of this action is not fully understood. In this study we investigated the mechanism by which lovastatin induces apoptosis using HepG2 human hepatoblastoma cells. Lovastatin induced apoptotic cell death in a dose-dependent manner in the cells, assessed by the flow cytometric analysis. Treatment with mevalonic acid, a precursor of cholesterol, did not significantly suppress the lovastatin-induced apoptosis. Lovastatin induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and apoptosis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blocked these actions of lovastatin. In addition, the lovastatin-induced apoptosis was significantly reduced by a calpain inhibitor, a broad spectrum caspase inhibitor z-VAD-fmk and inhibitors specific for caspase-9 and caspase-3 (z-LEHD-fmk and z-DEVD-fmk, respectively), but not by an inhibitor specific for caspase-8 (z-IETD-fmk). Collectively, these results suggest that lovastatin induced apoptosis of HepG2 hepatoma cells through intracellular $Ca^{2+}$ release and calpain activation, leading to triggering mitochondrial apoptotic pathway. These results further suggest that lovastatin may be valuable for the therapeutic management of human hepatoma.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.233-239
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• 2001

Local drug delivery by using biocompatible polymers has been developed in the treatment of periodontitis for many years. In the field of dental therapy, doxycycline is usually a first choice because of its broad-spectrum antibiotic activity. The strip releases antibiotics for a week, and the polymer should be degradable after a week. In this study, we prepared and evaluated the chitosan strips and nanoparticle strips containing doxycycline hydrochloride, and studied their antiacterial activity, dissoultion, and degrability in vitro. The weight of cast strip containing a 5 mg of doxycycline hydrochloride and a 45 mg of chitosan polymer was $57.67{\pm}0.17\;mg$. The release rate of doxycycline hydrochloride from the strip was measured by HPLC. The drug released from chitosan strip and nanoparticle strip was shown to be $50\;{\mu}g/mL$ in first 24 hours. In antibacterial test showed growth inhibitory activity after 24 hrs anaerobic incubation. In vitro degradability showed demolished weight of $93.74{\pm}0.08%$ chitosan strip, $82.48{\pm}1.29%$ chitosan nanoparticle strip, $2.47{\pm}1.99%$ polycarprolactione strip (control). These results showed that, with this doxycycline hydrochloride strip, it is feasible to obtain a sustained release of the drug within the periodontal pocket for seven days which may be improve for local drug delivery system for treatment of periodontal disease.

• Phonetics and Speech Sciences
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• v.4 no.2
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• pp.61-70
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• 2012

The current study observes the durational interaction of tautosyllabic consonants and vowels in the word-initial position of English and Korean child-directed speech (CDS). The effect of phonological laryngeal contrasts in stops on the following vowel duration, and the effect of the intrinsic vowel duration on the release duration of preceding stops in addition to the acoustic realization of the contrastive segments are explored in different prosodic contexts - phrase-initial/medial, focal accented/non-focused - in a marked speech style of CDS. A trade-off relationship between Voice Onset Time (VOT), as consonant release duration, and voicing phonation time, as vowel duration, reported from adult-to-adult speech, and patterns of durational variability are investigated in CDS of two languages with different linguistic rhythms, under systematically controlled prosodic contexts. Speech data were collected from four native English mothers and four native Korean mothers who were talking to their one-word staged infants. In addition to the acoustic measurements, the transformed delta measure is employed as a variability index of individual tokens. Results confirm the durational correlation between prevocalic consonants and following vowels. The interaction is revealed in a compensatory pattern such as longer VOTs followed by shorter vowel durations in both languages. An asymmetry is found in CV interaction in that the effect of consonant on vowel duration is greater than the VOT differences induced by the vowel. Prosodic effects are found such that the acoustic difference is enhanced between the contrastive segments under focal accent, supporting the paradigmatic strengthening effect. Positional variation, however, does not show any systematic effects on the variations of the measured acoustic quantities. Overall vowel duration and syllable duration are longer in English tokens but involve less variability across the prosodic variations. The constancy of syllable duration, therefore, is not found to be more strongly sustained in Korean CDS. The stylistic variation is discussed in relation to the listener under linguistic development in CDS.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.43 no.2
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• pp.165-174
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• 2017

This study reports a synthesis of an amphiphilic linear block copolymer consisting of a hydrophobic poly (lactide) (PLA) block and a hydrophilic hyperbranched polyglycerol (hbPG) block, PLA-b-hbPG. Simple chemical modification of the hbPG block with 4-hydroxycinnamic acid (CA) led to a photo-crosslinkable block copolymer, PLA-b-hbPG-CA. Nanosized micelles of the block copolyemrs were used as drug carriers for sustainable release. The hbPG shell made of a small molecular weight hbPG block showed excellent hydrophilicity, which can minimize in vivo toxicity. The UV-crosslinked PLA-b-hbPG-CA micelles loaded with drugs colud be served as a drug delivery carrier for its biocompatibility and self-assembled structures.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.479-488
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• 2021

This study aimed to develop docetaxel (DTX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC₅₀ values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

• BMB Reports
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• v.57 no.2
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• pp.71-78
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• 2024

Melanoma is one of the most aggressive skin tumors, and conventional treatment modalities are not effective in treating advanced melanoma. Although immunotherapy is an effective treatment for melanoma, it has disadvantages, such as a poor response rate and serious systemic immune-related toxic side effects. The main solution to this problem is the use of biological materials such as hydrogels to reduce these side effects and amplify the immune killing effect against tumor cells. Hydrogels have great advantages as local slow-release drug carriers, including the ability to deliver antitumor drugs directly to the tumor site, enhance the local drug concentration in tumor tissue, reduce systemic drug distribution and exhibit good degradability. Despite these advantages, there has been limited research on the application of hydrogels in melanoma treatment. Therefore, this article provides a comprehensive review of the potential application of hydrogels in melanoma immunotherapy. Hydrogels can serve as carriers for sustained drug delivery, enabling the targeted and localized delivery of drugs with minimal systemic side effects. This approach has the potential to improve the efficacy of immunotherapy for melanoma. Thus, the use of hydrogels as drug delivery vehicles for melanoma immunotherapy has great potential and warrants further exploration.

• Archives of Craniofacial Surgery
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• v.21 no.2
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• pp.127-131
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• 2020

A 60-year-old woman with a history of diabetes mellitus and chronic renal failure was admitted to the hospital with severe pain in the upper lip, which began 4 days prior to admission, accompanied by a bullous lesion and suspected cellulitis in the upper lip. Immediately after admission, as the patient's general condition worsened, tests revealed a non-ST elevated myocardial infarction, septic embolism of the lung, as well as septic shock. Her upper lip suddenly presented a gangrenous and necrotic change, which the tissue and blood culture confirmed to be a Klebsiella pneumoniae infection. After a quick response, the patient's general condition improved. Subsequently, serial debridement was performed to effectively clear away the purulent discharge. While under general anesthesia, the process confirmed full-layer necrosis of the upper lip including the orbicularis oris muscle. Almost half of the entire upper lip sustained a full-layer skin and soft tissue defect, with scar contracture. Six months later, to correct the drooling and lip sealing following the defects, a scar release and an Abbe flap coverage were performed considering both functional and aesthetic aspects. The follow-up revealed a favorable corrective result of the upper lip drooling, and the patient was satisfied from a functional perspective.

• YAKHAK HOEJI
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• v.42 no.3
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• pp.274-274
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• 1998

Aclarubicin(ACL)-entrapped freeze dried liposomes were prepared using Microfludizer to attain a sustained release at targeted organs in a prolonged time so that it can reduce th e side effect and maximize the therapeutic effect. The freeze-dried liposomes were evaluated for pharmacokinetics, antitumor activity against Sarcoma 180, cytotoxicity against L1210 and A549 tumor cells, spleen toxicity and myelosuppressive action. The AUC0->8hr values were 122+/-42, 382+/-140, 419+/-171, 835+/-206 and 443+/-309mcg min/ml for free ACL. ACL-liposome formulation I, II, III and IV, respectively. Cytotoidcity of ACL-entrapped liposomes against L1210 and A549 tumor cells was 2-4 times higher than that of free aclarubicin. ACL-liposome formulation I(PC/CHOL/TA) showed the most potent antitumor activity against Sarcoma 180 in mice. The loss of body weight was much smaller with ACL-entrapped liposomes than free ACL after I.p. injection at a dose of 2 mg/kg/day. Compared to free ACL, ACL-entrapped liposomes expressed a lower and delayed spleen toxicity up to 5th day after I.v. administration. Myelosupperssion seemed to be lower with ACL-entrapped liposome of PC/PC-hydrate/CHOL/TA (formulation III) than free aclarubicin.

• Journal of Veterinary Clinics
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• v.8 no.2
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• pp.157-170
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• 1991

Effects of recombinant bovine somatotropln(${\gamma}$BST) on hematologie and blood chemical values were investigated in twenty-five multiparous Holstein dairy cows. Recombinant BST was administered by two different routes ; intramusculary(12.5mg and 25mg/day) and subcutaneously(500mg and 750mg) in sustained-release vehicle every 2 weeks beginning 4 weeks postpartum and continuing for 7 months. Whole blood and serum samples were collected 0, 1, 2, 3, 5, and 7 months after beginning of treatments from control and ${\gamma}$BST-administered groups. Hematologic values including RBC, PCV, HB, MCH, MCHC, WBC and differential counts of treatment groups receiving ${\gamma}$BST were similiar to those of control group. Blood chemical values observed were total protein, albumin, A/G ratio, glucose, cholesterol, Ca, Pi, Ca/pi ratio, total bilirubin, creatinine, BUN, alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. There were no significant differences in blood chemical values of cows administered with ${\gamma}$BST from those of control. Although some blood chemical values were fluctuated at a certain observation period, they were remained within the normal physiological ranges. It is concluded from the observations of these experiments that the dose and dosage froms of ${\gamma}$BST employed in this work might not affect hematologic and blood chemical values in dairy cows under the normal sanitary condition and adequate nutritional balance.