CAJ | 학술논문

目的研制32P-磷酸铬-聚L-乳酸(CP-PLLA)缓释粒子,探讨不同配比对其理化性能的影响及植入正常小鼠肌肉后的放射性生物分布及作用特点等.方法应用压制法制备32P-CP-PLLA缓释粒子,比较不同相对分子质量PLLA、不同原料配比制备粒子的体外溶蚀失重率、放射性释出率(RRR)及放射性自吸收系数(RSAC);采用经皮穿刺法将相同表面活度的32P-CP-PLLA缓释粒子和32P-CP胶体植入和注射至正常小鼠小腿肌肉组织,观察小鼠体内放射性生物分布、有效半衰期、作用特点和粒子体内失重率、RRR.用SPSS 12.0软件,多个样本均数比较行单因素方差分析,组间两两比较行t检验.结果 32P-CP-PLLA粒子为淡绿色圆柱体,形态圆整,质量及粒子内放射性分布均匀;RSAC受PLLA相对密度影响较小,随PLLA相对分子质量增大而增加;体外RRR随PLLA的相对分子质量逐渐增加而降低,随PLLA和CP胶体质量比增加而增加,比值为3:1时达峰值,然后逐渐降低,同时粒子脆性逐步增加.32P-CP-PLLA粒子肌肉植入后,体内失重率及RRR缓慢增加,以RRR增加尤为迅速,且释出32P-CP主要分布于粒子邻近肌肉组织,肝、脾和粒子侧骨骼每克组织百分注射剂量率(%ID/g)值为1.7887,1.6401和1.9470,明显低于胶体组(4.7523,3.9712和4.3174,t均>2.7,P均<0.05),其他脏器%ID/g值极低,峰值与胶体组差异无统计学意义(t均<0.65,P均>0.05),植入靶位有效半衰期达13 d.放射性粒子周围弥漫性变性坏死区内未见正常肌肉纤维存在,肝、脾等重要脏器未见明显异常.结论 32P-CP-PLLA通过自身溶蚀降解缓慢释出放射性,有效提高了植入靶位放射性滞留量和有效半衰期,有效射程内具有集中的生物学效应,可增加应用剂量、提高局部生物学效应并减轻对重要脏器的毒性和不良反应.
목적 연제32P-린산락-취L-유산(CP-PLLA)완석입자,탐토불동배비대기이화성능적영향급식입정상소서기육후적방사성생물분포급작용특점등.방법 응용압제법제비32P-CP-PLLA완석입자,비교불동상대분자질량PLLA、불동원료배비제비입자적체외용식실중솔、방사성석출솔(RRR)급방사성자흡수계수(RSAC);채용경피천자법장상동표면활도적32P-CP-PLLA완석입자화32P-CP효체식입화주사지정상소서소퇴기육조직,관찰소서체내방사성생물분포、유효반쇠기、작용특점화입자체내실중솔、RRR.용SPSS 12.0연건,다개양본균수비교행단인소방차분석,조간량량비교행t검험.결과 32P-CP-PLLA입자위담록색원주체,형태원정,질량급입자내방사성분포균균;RSAC수PLLA상대밀도영향교소,수PLLA상대분자질량증대이증가;체외RRR수PLLA적상대분자질량축점증가이강저,수PLLA화CP효체질량비증가이증가,비치위3:1시체봉치,연후축점강저,동시입자취성축보증가.32P-CP-PLLA입자기육식입후,체내실중솔급RRR완만증가,이RRR증가우위신속,차석출32P-CP주요분포우입자린근기육조직,간、비화입자측골격매극조직백분주사제량솔(%ID/g)치위1.7887,1.6401화1.9470,명현저우효체조(4.7523,3.9712화4.3174,t균>2.7,P균<0.05),기타장기%ID/g치겁저,봉치여효체조차이무통계학의의(t균<0.65,P균>0.05),식입파위유효반쇠기체13 d.방사성입자주위미만성변성배사구내미견정상기육섬유존재,간、비등중요장기미견명현이상.결론 32P-CP-PLLA통과자신용식강해완만석출방사성,유효제고료식입파위방사성체류량화유효반쇠기,유효사정내구유집중적생물학효응,가증가응용제량、제고국부생물학효응병감경대중요장기적독성화불량반응.
Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.