pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers.

pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by 1H, 13C {H}, 31P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers.

Enhanced Physical Stability of L-Ascorbic Acid in an Ionic Liquid.

Ionic liquid (IL) technology was used to enhance the stability of L-ascorbic acid (AA). Pyridoxine was selected as the counter cation for anionic AA in IL. After AA was dissolved in water at 40 °C, its ratio decreased to 3.2% after 7 d. In contrast, the IL formulation showed negligible degradation, with almost no loss of AA even after 28 d. These results suggest that the use of IL enhances the stability of AA.

Design of Ionic Liquid Formulations with Azone-Mimic Structures for Enhanced Drug Skin Permeation.

Although laurocapram (Azone) significantly enhances the skin permeation of drugs, its development was hindered by its skin irritation. We then developed an Azone-mimic ionic liquid (IL-Azone), composed of less irritating cationic ε-caprolactam and anionic myristic acid. IL-Azone dissociates to the original cation and anion in the presence of water in the formulation. We tried to select a formulation suitable for IL-Azone in the present study. Each formulation contained 5 % of either Azone or IL-Azone along with the model drug antipyrine, and skin permeation experiments of the drug were conducted. The results revealed that IL-Azone did not enhance skin permeation when combined with most formulations tested. However, a notable and rapid enhancement in skin permeation was observed when combined with white petrolatum. This effect could be attributed to the minimal water content in white petrolatum, which prevented IL-Azone degradation. Furthermore, its permeation-enhancing effects from IL-Azone in white petrolatum were more pronounced and rapid than Azone. The rapid onset observed with IL-Azone can be attributed to its degradation into its original components at the interface between the stratum corneum and the living epidermis, which results in a shorter lag time before achieving a steady-state concentration in the SC compared to Azone.

Phosphoric Acid Triester Micelles: Characterization and Self-Assembly.

In this study, we analyzed the properties of amphiphilic alkyldi(methoxy poly(ethylene glycol) (MePEG)350-lactate) phosphates based on ethyl lactate, the monomethyl ether of poly(ethylene glycol)350, and alkyldichloro phosphates. Interestingly, these triesters combine two biodegradable bonds, -P(O)-O-C and -C(O)-O-C-, and include hydrophilic (MePEG350-lactate) and hydrophobic (R-aliphatic chain of alcohols) moieties. The properties of these esters resemble those of phospholipids. After being placed in an aqueous solution, they self-assembled. We also determined the effects of ester composition on micelle formation, stability, and size using dynamic light scattering. Solubilization tests using Sudan III or doxorubicin hydrochloride (Dox·HCl) revealed that they could be incorporated into the hydrophobic cores of dodecyl di(MePEG350-lactate) phosphate and hexadecyl di(MePEG350-lactate) phosphate. Notably, dodecyl di(MePEG350-lactate) phosphate was stable for five days, whereas hexadecyl di(MePEG350-lactate) phosphate was stable for seven days in phosphate-buffered saline. Moreover, Dox·HCl release rates from the micelles were approximately 30-40, 70-80, and 90-100% after 1, 5, and 28 d, respectively.

Synthesis and Characterization of Amphiphilic Diblock Polyphosphoesters Containing Lactic Acid Units for Potential Drug Delivery Applications.

Multistep one-pot polycondensation reactions synthesized amphiphilic diblock polyphosphoesters containing lactic acid units in the polymer backbone. At the first step was synthesized poly[poly(ethylene glycol) H-phosphonate-b-poly(ethylene glycol)lactate H-phosphonate] was converted through one pot oxidation into poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate]s. They were characterized by 1H, 13C {H},31P NMR, and size exclusion chromatography (SEC). The effects of the polymer composition on micelle formation and stability, and micelle size were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophobic alcohols. Drug loading and encapsulation efficiency tests using Sudan III and doxorubicin revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer micelles. The micelle size was 72-108 nm when encapsulating Sudan III and 89-116 nm when encapsulating doxorubicin. Loading capacity and encapsulation efficiency depend on the length of alkyl side chains. Changing the alkyl side chain from 8 to 16 carbon atoms increased micelle-encapsulated Sudan III and doxorubicin by 1.6- and 1.1-fold, respectively. The results obtained indicate that these diblock copolymers have the potential as drug carriers.

Design of an Ante-enhancer with an Azone-Mimic Structure using Ionic Liquid.

PURPOSE: Laurocapram (Azone) was broadly examined as a representative enhancer of skin penetration in the 1980s. However, it was not approved for treatment because it caused skin irritation following its penetration into the epidermis through the stratum corneum. In the present study, a so-called ante-enhancer with an Azone-mimic structure was designed based on an ante-drug with negligible systemic toxic effects following its permeation through the skin. METHODS: The ante-enhancer was designed using ionic liquid technology: an ionic liquid-type ante-enhancer (IL-Azone) with an Azone-mimic structure was prepared from ε-caprolactam and myristic acid as cationic and anionic substances, respectively. The enhancing effects of IL-Azone on the permeation by the following model drugs through pig skin were examined: isosorbide 5-mononitrate (ISMN), antipyrine (ANP), and fluorescein isothiocyanate dextran (FD-4). Skin irritation by IL-Azone was assessed using the Draize method. RESULTS: The primary irritation index (P.I.I.) of IL-Azone by the Draize method was markedly lower than that of Azone (6.9). Although the ability of IL-Azone to enhance skin penetration was not as high as Azone, IL-Azone moderately increased skin permeation by the model compounds tested (ISMN: 4.7 fold, ANP: 4.5 fold, FD-4: 4.0 fold). CONCLUSIONS: These results suggest the usefulness of designing a skin penetration enhancer using ionic liquid technology. Further trials on the ionic liquid design with an Azone-mimic structure using other cations and anions may lead to the development of better ante-enhancers.

Remote-controllable dosage management through a wearable iontophoretic patch utilizing a cell phone.

With regard to medical treatment through operations, remote control is possible, however, the area of remote-controllable drug treatment is yet to be established. In this study, a prototyped remote-controllable dosage management system that allows patients and caregivers to administer therapeutic drugs via an internet line without touching the dosage device or formulation was developed. This system consists of a transmitter (System A) located away from the patient, and a dosage device (System B) equipped with a receiver (B1), dosage management unit (B2), and a drug treatment unit (B3) that can be installed on the patient. Additionally, Bluetooth® is adopted to communicate from System A to System B. In the present study, System A was incorporated into a cell phone, and System B was a constant-current iontophoresis (IP) device, which was applied on excised pig skin. Sodium salt of betamethasone phosphate (BP-Na+) was selected as a model drug, and the in vitro skin permeation of BP- was evaluated. As a result, by transmitting the administration information incorporated in System A through B1 to B2, the optimal current was passed between the IP electrodes in B3, and the skin permeation of BP- was obtained by remote control. That is, the skin permeation of BP- was obtained by the current flowing from the IP device. The permeation amount decreased when the voltage load was stopped. These results suggested that remote control from System A enables dosing management of bioactive substances from dosage devices applied on the skin, intracutaneously, or subcutaneously without being near the patient. Although various trials are still required to complete the remote-controlled system, the patient does not have to go to the hospital except to take injections. Such drug administrations would lead to decreased medical expenses and increased quality of life for patients.

Chitosan-coated PLGA nanoparticles for transcutaneous immunization: Skin distribution in lysozyme-sensitized mice.

The effect of transcutaneous immunization was studied using a combined system of poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and iontophoresis (IP). Both hen egg-white lysozyme (HEL)-loaded PLGA nanoparticles coated with chitosan hydroxypropyltrimonium chloride and their fluorescent nanoparticles were prepared using an antisolvent diffusion method. Their mean volume diameters were 87.6 ± 38.9 nm and 84.9 ± 27.6 nm, respectively. It was suggested from the results of the ex vivo skin accumulation study using fluorescent nanoparticles that the HEL released from the nanoparticles to the skin surface was efficiently delivered to antigen-presenting cells. HEL-specific IgG1 and IgG2a titers were determined in an in vivo percutaneous immunoreactivity study using lysozyme-sensitized mice. As results, the group using nanoparticles and IP showed 1.33 times higher HEL-specific IgG1 titer than a sham treatment group. The HEL-specific IgG2a titer was 1.36 times higher in the nanoparticles and IP group than in the HEL solution and IP group. It was suggested from the quantification results of total IgE in serum that the combined use of PLGA nanoparticles and IP reduced the total IgE concentration. The level of cytokines may have decreased due to Th1 cell activation and relative suppression of Th2 cells. The cytokine level is presumed to be reduced by activation of Th1 cells and relative suppression of Th2 cells. The histamine amount in plasma and rectal temperature after the induction of anaphylactic shock using lysozyme-sensitized mice were also studied, which indicates that the combined use of PLGA nanoparticles and IP may provide the same therapeutic effect as an injection.

Effects of Physicochemical Properties of Constituent Ions of Ionic Liquid on Its Permeation through a Silicone Membrane.

Ionic liquids (ILs), defined as liquid salts composed of anions and cations, have the advantage of allowing constituent ions to be stably absorbed through biological membranes, such as skin. However, limited information is currently available on the effects of the physicochemical properties of constituent ions on the membrane permeation of ILs. Therefore, we herein investigated the effects of the polarity of constituent cations on the membrane permeation of each constituent ion from IL. Various ILs were prepared by selecting lidocaine (LID) as a cation and a series of p-alkylbenzoic acids with different n-octanol/water partition coefficients (Ko/w) as anions. These ILs were applied to a skin model, a silicone membrane, and membrane permeability was investigated. The membrane permeabilities of p-alkylbenzoic acids from their single aqueous suspensions were also measured for comparison. The membrane permeability of p-alkylbenzoic acid from the aqueous suspension increased at higher Ko/w. However, the membrane permeability of ILs was similar regardless of the Ko/w of the constituent p-alkylbenzoic acid. Furthermore, the membrane permeability of the counterion LID remained unchanged regardless of the constituent p-alkylbenzoic acid. These results suggest that even when the Ko/w of IL constituents markedly differs, the resulting IL does not affect membrane permeability.

A Mouse Model for Tuberculosis Combined With Inhalable Imiquimod-PLGA Nanocomposite Particles Based on Macrophage Phenotype.

BACKGROUND/AIM: In vivo models of tuberculosis are effective tools for developing new drugs. The objective of this study was to prepare in vivo models for tuberculosis by utilizing nanocomposite particles (NCPs) containing imiquimod-loaded poly(lactic-co-glycolic acid) nanoparticles. MATERIALS AND METHODS: NCPs were prepared from dichloromethane with imiquimod and poly(lactic-co-glycolic acid) using a spray dryer. Mice were treated with NCPs in the lungs by inhalation, and then infection with Mycobacterium bovis bacille Calmette-Guerin was performed (treatment groups). The concentrations of the pro-inflammatory cytokines, tumor necrosis factor-α and interferon-γ were measured in bronchoalveolar lavage fluid using an enzyme-linked immunosorbent assay. RESULTS: When animals were treated with NCPs, the concentrations of tumor necrosis factor-α and interferon-γ in bronchoalveolar lavage fluid were significantly higher than in animals not treated with NCPs. In addition, high bacterial counts and circular granuloma were observed. CONCLUSION: NCPs prepared in this study enhanced the level of inflammation in the lungs and support the preparation of in vivo models of tuberculosis.

Thermoresponsive Polyphosphoester via Polycondensation Reactions: Synthesis, Characterization, and Self-Assembly.

Using a novel strategy, amphiphilic polyphosphoesters based on poly(oxyethylene H-phosphonate)s (POEHP) with different poly(ethylene glycol) segment lengths and aliphatic alcohols with various alkyl chain lengths were synthesized using polycondensation reactions. They were characterized by 1H NMR, 13C {H} NMR 31P NMR, IR, and size exclusion chromatography (SEC). The effects of the polymer structure on micelle formation and stability, micelle size, and critical micelle temperature were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophilic PEG and hydrophobic alcohols. A solubilizing test, using Sudan III, revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer associates. Loading capacity depends on the length of alkyl side chains. The results obtained indicate that these structurally flexible polymers have the potential as drug carriers.

Primary Dural Mucosa-associated Lymphoid Tissue Lymphoma Mimicking Falx Meningioma: A Case Report.

An 85-year-old woman presented with ataxia and deterioration of cognitive functions. She had no history of autoimmune diseases or viral infections. Magnetic resonance imaging showed a solitary mass lesion at the cerebral falx on contrast-enhanced T1-weighted imaging. Gross total resection of the lesion involving the dura mater was performed by bifrontal craniotomy. Histological examination showed diffuse infiltration of small lymphocytes and plasma cells. There was also some proliferation of large lymphocytes with folded nuclei, high-density chromatin, and inconspicuous nucleoli. The large atypical B lymphocytes did not demonstrate diffuse dense sheet findings. Meningothelial components were not detected. Immunohistochemistry was positive for pan B-cell antigens. The analysis of the kappa/lambda ratio indicated kappa immunoglobulin light chain-restricted B-cell proliferation. The final histopathological diagnosis was mucosa-associated lymphoid tissue lymphoma. Systemic screening examinations were then performed. Histological findings of the bone marrow showed normal findings without atypical lymphocytes. A chromosomal study of the bone marrow showed 46, XX. 18F fluoro-2-deoxyglucose positron emission tomography showed high accumulations at the left pterygoid muscle and the right transverse processes of the thoracic vertebrae, and mild accumulation at the right ilium bone, which indicated disseminated lesions. One year later, thickening of the dura mater was detected. Therefore, gamma knife surgery was performed. Two years later, she was alive without neurological deterioration, and magnetic resonance imaging showed no evidence of recurrence.

Preparation of Micelles Encapsulating Doxorubicin and Their Anticancer Effect in Combination With Tranilast in 3D Spheroids and In Vivo.

BACKGROUND/AIM: The objective of this study was to prepare doxorubicin encapsulated in micelles (DOX-micelles) using poly(hexadecanyloxyethylene glycol-lactate phosphate), which we recently synthesized, and to evaluate the anticancer effect of DOX-micelles in vitro and in vivo. MATERIALS AND METHODS: To evaluate the anticancer effect of DOX-micelles in vitro, three-dimensional spheroids composed of B16 mouse melanoma cells and fibroblasts were prepared by changing the ratio of cancer cells to fibroblasts. In addition, for efficient doxorubicin treatment of the cells present in the center of the spheroids, tranilast, an anti-fibrotic drug was added to the spheroids before treatment with DOX-micelles, then the amount of doxorubicin and cell viability of spheroids were evaluated. Moreover, to assess the effects of the combination of DOX-micelles with tranilast in vivo, relative tumor volume was investigated in a mouse model of melanoma. RESULTS: The mean diameter and doxorubicin content of DOX-micelles were 93.3 nm and 3.5%, respectively. When the ratio of cancer cells to fibroblasts was 20:80, spheroids with spherical and rigid shapes were obtained. In addition, the amount of doxorubicin in the spheroids was increased by tranilast treatment, and an efficient anticancer effect was also observed. The anticancer effect of the combination of tranilast and DOX-micelles was confirmed in vivo. CONCLUSION: Micelles encapsulating doxorubicin are promising for cancer therapy, and their anticancer effect is improved by tranilast pretreatment in 3D spheroids in vivo.

Poly(Alkyloxyethylene-Lactate Phosphate) for Delivery of Doxorubicin: Synthesis and Characterization.

BACKGROUND/AIM: Serious side effects are associated with the use of doxorubicin. Nanoparticles as carriers for anticancer drugs are useful for reducing side effects and improving therapeutic effects. In this study, a polymer for preparing doxorubicin-containing nanoparticles was developed. Using a novel strategy, a biodegradable poly(oxyethylene glycol lactate H-phosphonate) based on dimethyl H-phosphonate and poly(ethylene glycol)-lactate (PEG-lactate) was synthesized. MATERIALS AND METHODS: Poly(hexadecanyloxyethylene - lactate phosphate) was obtained via chlorination of poly(oxyethylene glycol - lactate H-phosphonate) with trichloroisocyanuric acid and the addition of 1-hexadecanol. The polymer was characterized by 1H NMR and 31P NMR. RESULTS: The results of 1H NMR and 31P NMR showed that the polymer was successfully synthesized, and the yield was 46.9%. CONCLUSION: Poly(hexadecanyloxyethylene - lactate phosphate) has potential as a drug carrier.

Effects of lower alcohols on nanocomposite particles for inhalation prepared using O/W emulsion.

BACKGROUND: Inhalable nanocomposite particles using O/W emulsions were studied. The effect of the composition of the dispersed phase on the nanoparticles in the nanocomposite particles was reported, however, the effect on the inhalation characteristics of nanocomposite particles has not been investigated. OBJECTIVE: The aim of this study was to study the effects of lower alcohols in the dispersed phase of O/W emulsions on inhalable nanocomposite particles. METHODS: Nanocomposite particles were prepared using a spray dryer from O/W emulsion. A mixed solution of dichloromethane and lower alcohols in which rifampicin (RFP) and poly(L-lactide-co-glycolide) were dissolved was used as a dispersed phase, and an aqueous solution in which arginine and leucine were dissolved was used as a continuous phase. RESULTS: We succeeded in preparing non-spherical nanocomposite particles with an average diameter of 9.01-10.91 µm. The results of the fine particle fraction (FPF) measurement showed that the higher the hydrophobicity of the lower alcohol mixed in the dispersed phase, the higher the FPF value. The FPF value of the nanocomposite particles was significantly increased by using ethanol and 1-propanol. CONCLUSIONS: The results were revealed that mixing 1-propanol with the dispersed phase increased the amount of RFP delivered to the lungs.

Therapeutic Effects of GGsTop® Gel in a Mouse Model of 5-Fluorouracil-induced Oral Mucositis With Reduced White Blood Cells.

BACKGROUND/AIM: In order to produce an animal model for oral mucositis induced by anticancer drugs, it is necessary to maintain an immunosuppressive state. We determined the optimal dose and frequency of 5-fluorouracil for a model mouse production. In addition, we used this model to investigate the effect of GGsTop® gelation on the therapeutic effect of oral mucositis. MATERIALS AND METHODS: Changes in body weight and white blood cell count were measured to determine the optimal dosing schedule. The therapeutic effect of GGsTop® gel using chitosan was evaluated by observing changes in the ulcer area for three weeks and measuring collagen and glutathione concentrations in oral mucosal tissue. RESULTS: The optimal dose and frequency of 5-fluorouracil were found to be 50 mg/kg every four days. It was revealed that the therapeutic effect of GGsTop® was enhanced by gelation. CONCLUSION: GGsTop® gel is suggested to be a promising formulation for the treatment of oral mucositis.

Effects of Polyvinyl Alcohol on Drug Release from Nanocomposite Particles Using Poly (L-lactide-co-glycolide).

The effects of polyvinyl alcohol (PVA) on the release behavior of polymer nanoparticles from nanocomposite particles using amino acids were investigated. Rifaximin (RFX) was used as a hydrophobic drug model. RFX-loaded poly(L-lactide-co-glycolide) (PLLGA) nanoparticles were prepared using an antisolvent diffusion method. They were then spray-dried with equal amounts of amino acids to prepare the nanocomposite particles. The mean diameters of nanocomposite particles were 2.86-5.42 µm. The particle size increased as the concentration of PVA aqueous solution increased. The mean diameters of RFX-loaded PLLGA nanoparticles were 150-160 nm; however, the particle size distributions of those prepared using 0.25% (w/v) PVA aqueous solution differed significantly immediately after preparation and after redispersion from nanocomposite particles. The release test results of nanocomposite particles revealed that those prepared using 0.25% and 0.50% (w/v) aqueous PVA solutions rapidly released RFX. In contrast, particles prepared using 2.00 and 4.00% (w/v) PVA aqueous solution showed sustained drug release. The results of drug release tests of nanoparticles redispersed from nanocomposite particles showed that the nanoparticles prepared using 0.50% and 2.00% (w/v) PVA aqueous solution suppressed the initial burst. Therefore, we considered that the results of the drug release behavior of the nanoparticles in these particles reflectsreflect the release behavior of the nanoparticles from the nanocomposite particles. These results indicate that the rate of redispersion from nanocomposite particles to nanoparticles can be controlled by changing the concentration of PVA aqueous solution.

Effects of GGsTop® on Collagen and Glutathione in the Oral Mucosa Using a Rat Model of 5-Fluorouracil-Induced Oral Mucositis.

BACKGROUND/AIM: To evaluate the usefulness of GGsTop® for oral mucositis, a quantitative study focusing on oral mucosal tissues is necessary. In this study, we aimed to quantify collagen and glutathione using a rat model of 5-fluorouracil-induced oral mucositis. MATERIALS AND METHODS: Changes in ulcer area and erythrocyte count were measured to confirm the usefulness of GGsTop® for oral mucositis. The effect of GGsTop on collagen was evaluated by observing oral mucosal tissue sections and measuring the collagen concentration in the tissues. The total glutathione concentration and the oxidized glutathione concentration were measured, and the concentration of the reduced form was calculated. RESULTS: GGsTop® shortened the treatment period for oral mucositis without affecting the white blood cell count. In addition, GGsTop® promoted collagen production and alleviated oxidative stress conditions. CONCLUSION: GGsTop affects collagen and glutathione in the treatment of oral mucositis.

Effect of the Conformation of Poly(L-lactide-co-glycolide) Molecules in Organic Solvents on Nanoparticle Size.

Controlling the size of nanoparticles is important for drug delivery methods such as pulmonary administration, transdermal administration, and intravenous administration. In this study, we have investigated the effect of polymer conformation in organic solvents on the size of the nanoparticles. Poly(L-lactide-co-glycolide) (PLLGA), a promising nanoparticle carrier, was used as the polymer. A mixed solution of dichloromethane, which is a good solvent, and a lower alcohol (methanol, ethanol, and 1-propanol), which is a poor solvent, was used as the solvent for dissolving PLLGA. An oil-in-water emulsion was prepared by sonication using the mixed solution of organic solvents in which PLLGA was dissolved as a dispersed phase and an amino acid aqueous solution as a continuous phase. Nanocomposite particles were prepared from the emulsion using a spray dryer and redispersed in purified water to obtain the PLLGA nanoparticles. The conformation of PLLGA molecules in the organic solvents was evaluated by analyzing the results of the viscosity measurements. The polymer coil radius and the volume per polymer coil were observed to decrease with the increase in the ratio of the lower alcohol in the solvent, whereas these values tended to decrease with the use of more hydrophilic lower alcohols. In addition, based on the results of the calculated entanglement index, it was found that when the hydrophobicity of the dispersed phase is reduced, the polymers were hardly entangled with each other. These results were significant, specifically when the ratio of the lower alcohol in the solvent was low. Estimation of the Pearson's correlation coefficients indicated that there were positive correlations between these indices and the mean volume diameter of PLLGA nanoparticles. This study shows that changing the composition of the dispersed phase, in which the PLLGA is dissolved, can change the conformation of the PLLGA molecules and control the size of the PLLGA nanoparticles.

A Rat Model of Oral Mucositis Induced by Cancer Chemotherapy for Quantitative Experiments.

BACKGROUND/AIM: Oral mucositis, which occurs frequently in the treatment of cancer, is a major problem. In this study, we aimed to develop a rat model of oral mucositis induced by cancer chemotherapy for quantitative measurement. MATERIALS AND METHODS: A model animal of oral mucositis was prepared by injecting an acetic acid aqueous solution into the buccal mucosa of rats to which a 5-FU solution had been previously administered. The doses of 5-FU and acetic acid were examined, and a treatment experiment using Kenalog® was performed. RESULTS: The optimal dose of the 5-FU solution and the optimal concentration of the acetic acid aqueous solution were 40 mg/kg and 25%, respectively. Treatment with Kenalog® confirmed that this model mimics immunocompromised oral mucositis. CONCLUSION: Compared with a mouse model, oral mucositis can be easily observed in this model and provides a large amount of oral mucosal tissue.