본 연구의 목적은 겐타마이신 함유 스폰지인 겐타콜과 콜라템프를 랫드 근육내 이식 후 생체적합성을 비교하는 것이다. SD 랫드 66 마리를 네 그룹으로 나누었다; (1) 대퇴사두근에 무처치한 군 (대조군, 6 마리), (2) 대퇴사두근에 겐타마이신 액을 주사한 군 (겐타마이신 군, 6 마리), (3) 대퇴사두근에 콜라템프를 이식한 군 (콜라템프 군, 27마리), (4) 대퇴사두근에 겐타콜을 이식한 군 (겐타콜 군, 27 마리). 겐타콜과 콜라템프 이식 한근육 내 겐타마이신 농도는 시간이 지남에 따라 점차 감소하였다. 혈액 내에 겐타마이신 농도는 측정되지 않았다. 조직학적으로 겐타마이신액을 주사 후 근육 내에 다형핵백혈구, 림프구, 대식세포를 포함하는 염증세포가 중등도에서 심하게 침윤되었고, 경도에서 중등도의 근육내 부종이 관찰되었다. 그러나, 이러한 국소 자극의 조직학적 변화는 콜라템프와 겐타콜 군에서는 현저히 감소하였다. 이상의 결과, 겐타콜은 콜라템프와 비교하였을 때에 전신적인 영향을 미치지 않으며 국소자극의 정도가 유사하였고, 생체이용성이 유사하여 좋은 생체적합성을 가지는 것으로 생각된다.
본 연구의 목적은 겐타마이신 함유 스폰지인 겐타콜과 콜라템프를 랫드 근육내 이식 후 생체적합성을 비교하는 것이다. SD 랫드 66 마리를 네 그룹으로 나누었다; (1) 대퇴사두근에 무처치한 군 (대조군, 6 마리), (2) 대퇴사두근에 겐타마이신 액을 주사한 군 (겐타마이신 군, 6 마리), (3) 대퇴사두근에 콜라템프를 이식한 군 (콜라템프 군, 27마리), (4) 대퇴사두근에 겐타콜을 이식한 군 (겐타콜 군, 27 마리). 겐타콜과 콜라템프 이식 한근육 내 겐타마이신 농도는 시간이 지남에 따라 점차 감소하였다. 혈액 내에 겐타마이신 농도는 측정되지 않았다. 조직학적으로 겐타마이신액을 주사 후 근육 내에 다형핵백혈구, 림프구, 대식세포를 포함하는 염증세포가 중등도에서 심하게 침윤되었고, 경도에서 중등도의 근육내 부종이 관찰되었다. 그러나, 이러한 국소 자극의 조직학적 변화는 콜라템프와 겐타콜 군에서는 현저히 감소하였다. 이상의 결과, 겐타콜은 콜라템프와 비교하였을 때에 전신적인 영향을 미치지 않으며 국소자극의 정도가 유사하였고, 생체이용성이 유사하여 좋은 생체적합성을 가지는 것으로 생각된다.
The objective of this study was to compare the biocompatibility for local irritation and bioavailability of $Gentacol^{TM}$ and $Collatamp^{TM}$, after single intramuscular loading in rats. Sixty-six male Sprague-Dawley rats were divided into 4 groups; (1) any test materials we...
The objective of this study was to compare the biocompatibility for local irritation and bioavailability of $Gentacol^{TM}$ and $Collatamp^{TM}$, after single intramuscular loading in rats. Sixty-six male Sprague-Dawley rats were divided into 4 groups; (1) any test materials were not applied into the quadriceps muscles (control group, N = 6), (2) Gentamicin was injected into the quadriceps muscles (Gentamicin group, N = 6), (3) Collatamp was applied into the quadriceps muscles (Collatamp group, N = 27), and (4) Gentacol was applied into the quadriceps muscles (Gentacol group, N = 27). The concentration of gentamicin in muscles was gradually decreased with time after loaded in the both $Gentacol^{TM}$ and $Collatamp^{TM}$ loaded regions. No detectable gentamicin was observed in the plasma of $Gentacol^{TM}$ and $Collatamp^{TM}$ loaded rats. Histologically, moderate to severe inflammatory cell infiltrations including PMN, lymphoid cells and macrophages were observed with slight to moderate edematous changes of muscle fibers after intramuscular injection of gentamicin. However, these histopathological changes of gentamicin injection induced local irritations were dramatically decreases after intramuscular loading of $Collatamp^{TM}$ and $Gentacol^{TM}$. These results suggest $Gentacol^{TM}$ may show favorable local bioavailability and induce only slight local irritations as comparable as $Collatamp^{TM}$ without systemic exposures in the condition of this experiment.
The objective of this study was to compare the biocompatibility for local irritation and bioavailability of $Gentacol^{TM}$ and $Collatamp^{TM}$, after single intramuscular loading in rats. Sixty-six male Sprague-Dawley rats were divided into 4 groups; (1) any test materials were not applied into the quadriceps muscles (control group, N = 6), (2) Gentamicin was injected into the quadriceps muscles (Gentamicin group, N = 6), (3) Collatamp was applied into the quadriceps muscles (Collatamp group, N = 27), and (4) Gentacol was applied into the quadriceps muscles (Gentacol group, N = 27). The concentration of gentamicin in muscles was gradually decreased with time after loaded in the both $Gentacol^{TM}$ and $Collatamp^{TM}$ loaded regions. No detectable gentamicin was observed in the plasma of $Gentacol^{TM}$ and $Collatamp^{TM}$ loaded rats. Histologically, moderate to severe inflammatory cell infiltrations including PMN, lymphoid cells and macrophages were observed with slight to moderate edematous changes of muscle fibers after intramuscular injection of gentamicin. However, these histopathological changes of gentamicin injection induced local irritations were dramatically decreases after intramuscular loading of $Collatamp^{TM}$ and $Gentacol^{TM}$. These results suggest $Gentacol^{TM}$ may show favorable local bioavailability and induce only slight local irritations as comparable as $Collatamp^{TM}$ without systemic exposures in the condition of this experiment.
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문제 정의
The objective of this study was to examine the biocompatibility for local irritation and bioavailability of newly developed gentamicin impregnated sponge formulation, GentacolTM compared with commercial gentamicin impregnated sponge formulation, CollatampTM, after single intramuscular loading in rats.
제안 방법
After intramuscular injection of gentamicin, moderate to severe inflammatory cell infiltrations including PMN, lymphoid cells and macrophages were observed with slight to moderate edematous changes of muscle fibers at histopathological observations (Fig 1). However, these histopathological changes of gentamicin injection induced local irritations were dramatically decreased after intramuscular loading of two different sponge formulations, CollatampTM and GentacolTM(Fig 1).
Concentrations of gentamicin in the rat plasma and muscle samples were determined LC-MS/MS method. Chromatographic analysis was performed using an Agilent 1100 Series HPLC (Agilent Technologies, Palo Alto, CA, USA) equipped with on-line degasser, binary pump, autosampler and column compartment. Separation of the analyte from potentially interfering material was achieved at ambient temperature using VDSpher PUR100 C18-E columns (2.
The goal of this study was to compare newly developed gentamicin impregnated sponge formulation, GentacolTM with CollatampTM through bioavailability and biocompatibility test after single intramuscular loading in rats.
After paraffin embedding, 3 μm-thick sections were prepared and representative sections were stained with Hematoxylin and eosin (H&E) for light microscopically examination, and the histological profiles of individual muscle was observed under a light microscope (Nikkon; E400, Japan). To observe more detail histopathological changes, the semiquantative histological damage and edema scoring systems as indication of possible local irritation were applied based on the four degrees of scoring systems; 3+: Severe, 2+: Moderate, 1+: Slight, 0: not detected-normal appearances (Max = 3). In addition, the numbers of inflammatory cells, polymorphonuclear cells (PMNs), lymphoid and macrophages, were also counted in a restricted view fields (mm2) around loading surfaces using automated image analyzer (iSolution FL ver 9.
대상 데이터
Sixty-six male Sprague-Dawley rats (6-week-old, Daehan bio link, Eumseong, Korea) were used after acclimation for 7 days. Animals were housed three per polycarbonate cage in a temperature (20-25℃) and humidity (50-55%) controlled room.
데이터처리
Variance homogeneity was examined using the Levene test. If the Levene test indicated no significant deviations from variance homogeneity, the obtain data were analyzed by one way ANOVA test followed by Scheffe test to determine which pairs of group comparison were significantly different. When a significant difference is observed in the Kruskal-Wallis H test, the Mann-Whitney U (MW) test was conducted to determine the specific pairs of group comparison, which are significantly different.
이론/모형
A multiple comparison tests for different dose groups were conducted. Variance homogeneity was examined using the Levene test. If the Levene test indicated no significant deviations from variance homogeneity, the obtain data were analyzed by one way ANOVA test followed by Scheffe test to determine which pairs of group comparison were significantly different.
성능/효과
However, these histopathological changes of gentamicin injection induced local irritations were dramatically decreased after intramuscular loading of two different sponge formulations, CollatampTM and GentacolTM. Based on these results, it could be suggested that gentamicin injection related local irritations are reduced by gentamicin impregnated sponges formulations and that GentacolTM may induce only slight local irritations as comparable as CollatampTM in this our experiment.
Consequently, the scores of edema and inflammation significantly (p < 0.01) increased in gentamicin injected muscles as compared with intact control muscles, and infiltrated PMNs, lymphoid cells and macrophages between muscle fibers also significantly (p < 0.01) increased in this experiment.
Then, they were gradually decreased with time after loaded in the both GentacolTM and CollatampTM loaded regions. It was suggested that gentamicin was effectively well localized into loading sites by impregnated sponge formulations, and GentacolTM may show favorable local bioavailability as comparable as CollatampTM, at least, in the condition of this experiment.
No significant or meaningful changes on the body weight were detected in GentacolTM loaded rats as compared with CollatampTM loaded rats at each point measured in this study (Fig 1). All rats used in this experiment, showed normal body weight increases, ranged in normal age-matched rats regardless of treatment.
Body weight changes after single GentacolTM and CollatampTM loading. No significant or meaningful changes on the body weight were detected in GentacolTM loaded rats as compared with CollatampTM loaded rats at each point measured in this study. Values are expressed mean ± SD of three rats.
The results in this study suggested that gentamicin is well localized into around loading tissue and gentamicin related local irritations are reduced by impregnated sponge formulations (Collatamp and Gentacol) and GentacolTM may show favorable local bioavailability and induce only slight local irritations as comparable as CollatampTM without disquieting systemic exposures in the condition of this experiment.
참고문헌 (16)
Abdelbary G, El-Gendy N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech 2008; 9: 740-747.
Cabanes A, Reig F, Garcia-Anton JM, Arboix M. Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits. Res Vet Sci 1998; 64: 213-217.
Hayes G, Moens N, Gibson T. A review of local antibiotic implants and applications to veterinary orthopaedic surgery. Vet Comp Orthop Traumatol 2013; 26: 251-259.
Hwang MR, Kim JO, Lee JH, Kim YI, Kim JH, Chang SW, Jin SG, Kim JA, Lyoo WS, Han SS, Ku SK, Yong CS, Choi HG. Gentamicin-loaded wound dressing with polyvinyl alcohol/dextran hydrogel: gel characterization and in vivo healing evaluation. AAPS PharmSciTech 2010; 11: 1092-1103.
Lee HS, Cho HR, Yang KJ, Shin HD, Park BR, Jang HJ, Cho KW, Kim HD, Ku SK. Local irritation test of 3 types of ${\beta}$ -glucan after subcutaneous injection in rats. Lab Anim Res 2006; 22: 339-342.
Lovering AM, Sunderland J. Impact of soaking gentamicincontaining collagen implants on potential antimicrobial efficacy. Int J Surg 2012; 10: S2-4.
Megoulas NC, Koupparis MA. Development and validation of a novel LC/ELSD method for the quantitation of gentamicin sulfate components in pharmaceuticals. J Pharm Biomed Anal 2004; 36: 73-79.
Reynolds LF, Mailman TL, McMillan DD. Gentamicin in neonates at risk for sepsis - peak serum concentrations are not necessary. Paediatr Child Health 2012; 17: 310-312.
Robert M, Melanie J. Gentamicin: a great way to start. Aust Prescr 2010; 33: 134-135.
Rutten HJ, Nijhuis PH. Prevention of wound infection in elective colorectal surgery by local application of gentamicincontaining collagen sponge. Eur J Surg 1997; 578: 31-35.
Simpson JA, Peacock J, Maxwell-Armstrong C. Use of a gentamicin-impregnated collagen sheet (Collatamp $^{(R)}$ ) following implantation of a sacral nerve stimulator for faecal incontinence. Colorectal Dis 2012; 14: e200-202.
Singisetti KK, Ashcroft GP. Intramedullary delivery of Collatamp in long bone infections: a simple innovative technique. Ann R Coll Surg Engl 2009; 91: 437.
Stemberger A, Grimm H, Bader F, Rahn HD, Ascherl R. Local treatment of bone and soft tissue infections with the collagen-gentamicin sponge. Eur J Surg Suppl 1997; 578: 17-26.
Sundin DP, Sandoval R, Molitoris BA. Gentamicin inhibits renal protein and phospholipid metabolism in rats: implications involving intracellular trafficking. J Am Soc Nephrol 2001; 12: 114-123.
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