• Journal of Veterinary Science
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• v.23 no.1
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• pp.1.1-1.11
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• 2022

Background: The poor bioadhesion capacity of tilmicosin resulting in treatment failure for Staphylococcus aureus small colony variants (SASCVs) mastitis. Objectives: This study aimed to increase the bioadhesion capacity of tilmicosin for the SASCVs strain and improve the antibacterial effect of tilmicosin against cow mastitis caused by the SASCVs strain. Methods: Tilmicosin-loaded chitosan oligosaccharide (COS)-sodium carboxymethyl cellulose (CMC) composite nanogels were formulated by an electrostatic interaction between COS (positive charge) and CMC (negative charge) using sodium tripolyphosphate (TPP) (ionic crosslinkers). The formation mechanism, structural characteristics, bioadhesion, and antibacterial activity of tilmicosin composite nanogels were studied systematically. Results: The optimized formulation was comprised of 50 mg/mL (COS), 32 mg/mL (CMC), and 0.25 mg/mL (TPP). The size, encapsulation efficiency, loading capacity, polydispersity index, and zeta potential of the optimized tilmicosin composite nanogels were 357.4 ± 2.6 nm, 65.4 ± 0.4%, 21.9 ± 0.4%, 0.11 ± 0.01, and -37.1 ± 0.4 mV, respectively; the sedimentation rate was one. Scanning electron microscopy showed that tilmicosin might be incorporated in nano-sized crosslinked polymeric networks. Moreover, adhesive studies suggested that tilmicosin composite nanogels could enhance the bioadhesion capacity of tilmicosin for the SASCVs strain. The inhibition zone of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels were 2.13 ± 0.07, 3.35 ± 0.11, and 1.46 ± 0.04 cm, respectively. The minimum inhibitory concentration of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels against the SASCVs strain were 2, 1, and 1 ㎍/mL, respectively. The in vitro time-killing curves showed that the tilmicosin composite nanogels increased the antibacterial activity against the SASCVs strain. Conclusions: This study provides a potential strategy for developing tilmicosin composite nanogels to treat cow mastitis caused by the SASCVs strain.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.177-186
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• 1994

Bioadhesive microcapsules of cephalexin, using Eudragit RS/RL coated with polycarbophil or carbopol, were evaluated biopharmaceutically. The GI transit of microcapsules in rats was studied. Bioadhesive microcapsules coated with polycarbophil or carbopol were shown to have substantially longer GI transit time than Eudragit RS/RL microcapsule. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. Plasma drug levels in rabbits showed that bioadhesive microcapsules resulted in a longer duration of action and greater bioavailability than other microcapsule or drug powder. Thus, the principle of bioadhesion can significantly improve therapy, due to a reduced rate of gastric emptying, an increase in contact time, and the intimacy of contact of the drug with the absorbing membrane.

• Journal of Veterinary Science
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• v.23 no.3
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• pp.48.1-48.12
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• 2022

Background: The poor intracellular concentration of enrofloxacin might lead to treatment failure of cow mastitis caused by Staphylococcus aureus small colony variants (SASCVs). Objectives: In this study, enrofloxacin composite nanogels were developed to increase the intracellular therapeutic drug concentrations and enhance the efficacy of enrofloxacin against cow mastitis caused by intracellular SASCVs. Methods: Enrofloxacin composite nanogels were formulated by an electrostatic interaction between gelatin (positive charge) and sodium alginate (SA; negative charge) with the help of CaCl₂ (ionic crosslinkers) and optimized by a single factor test using the particle diameter, zeta potential (ZP), polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) as indexes. The formation mechanism, structural characteristics, bioadhesion ability, cellular uptake, and the antibacterial activity of the enrofloxacin composite nanogels against intracellular SASCVs strain were studied systematically. Results: The optimized formulation was comprised of 10 mg/mL (gelatin), 5 mg/mL (SA), and 0.25 mg/mL (CaCl₂). The size, LC, EE, PDI, and ZP of the optimized enrofloxacin composite nanogels were 323.2 ± 4.3 nm, 15.4% ± 0.2%, 69.6% ± 1.3%, 0.11 ± 0.02, and -34.4 ± 0.8 mV, respectively. Transmission electron microscopy showed that the enrofloxacin composite nanogels were spherical with a smooth surface and good particle size distributions. In addition, the enrofloxacin composite nanogels could enhance the bioadhesion capacity of enrofloxacin for the SASCVs strain by adhesive studies. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration were 2, 4, 4, and 8 ㎍/mL, respectively. The killing rate curve had a concentration-dependent bactericidal effect as increasing drug concentrations induced swifter and more radical killing effects. Conclusions: This study provides a good tendency for developing enrofloxacin composite nanogels for treating cow mastitis caused by intracellular SASCVs and other intracellular bacterial infections.

• Bulletin of the Korean Chemical Society
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• v.25 no.11
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• pp.1629-1630
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• 2004

• Korean Journal of Fisheries and Aquatic Sciences
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• v.44 no.6
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• pp.584-590
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• 2011

This study aimed to demonstrate the bioadhesive characteristics of gelatin biofilm to rat skin. The biofilm was manufactured from gelatin extracted from the acetic acid treated-skin of the yellowfin tuna Thunnus albacares. The bioadhesive strength of tuna gelatin biofilm was compared to that of porcine gelatin biofilm. The tuna gelatin biofilm exhibited a higher bioadhesive strength than the porcine gelatin biofilm. Gelatin biofilm was subjected to glutaraldehyde treatment at different concentrations, temperatures and pH in order to improve its bioadhesive strength. Glutaraldehyde treatment improved the bioadhesive strength of gelatin biofilm up to three-fold. The bioadhesive strength of glutaraldehyde treated-biofilm was significantly decreased by application of sodium borohydride.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.928-933
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• 2006

Percutaneous delivery of NSAIDs has advantages of avoiding hepatic first pass effect and delivering the drug for extended period of time at a sustained, concentrated level at the inflammation site that mainly acts at the joint and the related regions. To develop the new topical formulations of pranoprofen that have suitable bioadhesion, the gel was formulated using hydroxypropyl methylcellulose (HPMC) and poloxamer 407. The effects of temperature on drug release was performed at $32^{\circ}C$, $37^{\circ}C$ and $42^{\circ}C$ according to drug concentration of 0.04%, 0.08%, 0.12%, 0.16%, and 0.2% (w/w) using synthetic cellulose membrane at $37{\pm}0.5^{\circ}C$. The increase of temperature showed the increased drug release. The activation energy (Ea), which were calculated from the slope of lop P versus 1000/T plots was 11.22 kcal/ mol for 0.04%, 10.79 kcal/mol for 0.08%, 10.41 kcal/mol for 0.12% and 8.88 kcal/mol for 0.16% loading dose from the pranoprofen gel. To increase the drug permeation, some kinds of penetration enhancers such as the ethylene glycols, the propylene glycols, the glycerides, the non-ionic surfactants and the fatty acids were incorporated in the gel formulation. Among the various enhancers used, propylene glycol mono laurate showed the highest enhancing effects with the enhancement factor of 2.74. The results of this study suggest that development of topical gel formulation of pranoprofen containing an enhancer is feasible.

• Proceedings of the KOSOMBE Conference
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• v.1996 no.05
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• pp.223-225
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• 1996

Poly (ethylene glycol) (PEG)macromers terminated with acrylate groups and interpenetrating polymer networks(IPN) composed of poly(hydroxyethyl methacrylate)(PHEMA) or poly(hydroxyethyl methacrylate-co-hydropropyl methacrylate-co-N-vinyl pyrrolidone) [P(HEMA-co-HPMA-co-NVP)] and PEG macromer were synthesized with the aim of obtaining protein adsorption resisatnt soft contact lens. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Crosslinked P(HEMA) or P(HEMA-co-HPMA-co-NVP) chains were interpenetrated into the cross-linked three-dimensional networks of PEG. It was found that albumin adsorption onto the contact lens prepared by P(HWMA)/PEG IPN decreases with a decrease of molecular weight of PEG whereas its adsorption onto the contact lens prepared by P(HEMA-co-HPMA-co-NVP)/PEG IPN decreases with an increase of molecular weight of PEG. Also, it was found that albumin adsorption onto the both contact lens decreases with an increase of concentration of PEG macromer in the IPN preparation. There are also more adequate in the bioinertness and bioadhesion for the contact lens by P(HEMA)/PEG IPN or P(HEMA-co-HPMA-co-NVP)/PEG IPN than that by P(HEMA) or P(HEMA-co-HPMA-co-NVP).

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.357-363
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• 2011

In relieving local pains, ropivacaine has been widely used. In case of their application such as ointments and creams, it is difficult to expect their effects for a significant period of time, because they are easily removed by wetting, movement and contacting. Therefore, the new formulations that have suitable bioadhesion were needed to enhance local anesthetic effects. The effect of drug concentration and temperature on drug release was studied from the prepared 1.5% Carboxymethyl cellulose (CMC) (150MC) gels using synthetic cellulose membrane at $37{\pm}0.5^{\circ}C$. As the drug concentration and temperature increased, the drug release increased. A linear relationship was observed between the logarithm of the permeability coefficient and the reciprocal temperature. The activation energy of drug permeation was 3.16 kcal/mol for a 1.5% loading dose. To increase the skin permeation of ropivacaine from CMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the ropivacaine-CMC gels. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. For the efficacy study, the anesthetic action of the formulated ropivacaine gel containing an enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. According to the rat tail-flick test, 1.5% drug gels containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed the best prolonged local analgesic effects. In conclusion, the enhanced local anesthetic gels containing penetration enhancer and vasoconstrictor could be developed using the bioadhesive polymer.