• 1成都軍區(qū)昆明總醫(yī)院骨科 全軍創(chuàng)傷骨科研究所（昆明，650032）;;
  • 2昆明醫(yī)科大學(xué)研究生部;

目的對(duì)脂質(zhì)體作為抗生素載體的研究進(jìn)展作一綜述。 方法查閱近年國(guó)內(nèi)外有關(guān)脂質(zhì)體作為抗生素載體的文獻(xiàn)，并進(jìn)行總結(jié)分析。 結(jié)果脂質(zhì)體作為抗生素載體能顯著改善藥物藥代動(dòng)力學(xué)和生物學(xué)分布，對(duì)病變部位有靶向選擇性，能增強(qiáng)抗菌活性，減少抗生素在治療期間的毒副作用。但其存在物理、化學(xué)穩(wěn)定性不高及包封率低等問(wèn)題。 結(jié)論脂質(zhì)體作為抗生素載體能降低藥物毒性，改善藥物生物學(xué)分布和藥代動(dòng)力學(xué)，為延緩或避免細(xì)菌耐藥和徹底治愈感染性疾病帶來(lái)了曙光。

引用本文： 楊杜明,徐永清,李福兵,劉華. 脂質(zhì)體作為抗生素載體的研究進(jìn)展. 中國(guó)修復(fù)重建外科雜志, 2012, 26(11): 1387-1390. doi: 復(fù)制

1. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipid. J Mol Boil, 1965, 13(1): 238-252.
2. Gregoriadis G, Wills EJ, Swain CP, et al. Drug-carrier potential of liposomes in cancer chemotherapy. Lancet, 1974, 1(7870): 1313-1316.
3. 陸彬. 藥劑學(xué). 北京: 中國(guó)醫(yī)藥科技出版社, 2003: 454.
4. Drulis-Kawa Z, Dorotkiewicz-Jach A. Liposomes as delivery systems for antibiotics. Int J Pharm, 2010, 387(1-2): 187-198.
5. Shen Y, Ji Y, Xu S, et al. Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: preparation, characterization, and pharmacokinetics. Drug Deliv, 2011, 18(5): 361-366.
6. Cao J, Sun J, Wang X, et al. N-trimethyl chitosan-coated multivesicular liposomes for oxymatrine oral delivery. Drug Dev Ind Pharm, 2009, 35(11): 1339-1347.
7. Akiyama M. Slow change in the repeat period of multilamellar dimyristoyl phosphatidylcholine accompanied by thermal phase transition. Biochim Biophys Acta, 1981, 644(1): 89-95.
8. Bakker-Woudenberg IA. Long-circulating sterically stabilized liposomes as carriers of agents for treatment or for imaging ionfectious foci. Int J Antimicrob Agents, 2002, 19(4): 299-311.
9. Abeylath SC, Turos E. Drug delivery approaches to overcome bacterial resistence to beta-lactam antibiotics. Expert Opin Drug Deliv, 2008, 5(9): 931-949.
10. Jia Y, Joly H, Omri A. Liposomes as a carrier for gentamicin delivery: development and evaluation of the physicochemical properties. Int J Pharm, 2008, 359(1-2): 254-263.
11. Hamidi M, Azadi A, Rafiei P. Pharmacokinetic consequences of pegylattion. Drug Delive, 2006, 13(6): 399-409.
12. Schiffelers R, Storm G, Bakker-Woudenberg I. Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies. J Antimicrob Chemother, 2001, 48(3): 333-344.
13. Bakker-Woudenberg IA, Schiffelers RM, Storm G, et al. Long-circulating sterically stabilized liposomes in the treatment of infections. Methods Enzymol, 2005, 391: 228-260.
14. Beaulac C, Clement-Major S, Hawari J, et al. In vitro kinetics of drug release and pulmonary retention of microencapsulated antibiotic in liposomal formulations in relation to the lipid composition. J Microencapsul, 1997, 14(3): 335-348.
15. Ceh B, Winterhalter M, Frederik PM, et al. Stealth liposomes: from theory to product. Adv Drug Deliv Rev, 1997, 24(2): 165-177.
16. Bakker-Woudenberg IA, ten Kate MT, Guo L, et al. Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection. Antimicrob Agents Chemother, 2002, 46(8): 2575-2581.
17. Bakker-Woudenberg IA, ten Kate MT, Guo L, et al. Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated liposomes for treatment of Klebsiella pneumoniae pneumonia in rats. Antimicrob Agents Chemother, 2011, 45(5): 1487-1492.
18. Muppidi K, Wang J, Betageri G, et al. PEGylated liposome encapsulation increases the lung tissue concentration of vancomycin. Antimicrob Agents Chemother, 2011, 55(10): 4537-4542.
19. Tomioka H, Saito H, Sato K, et al. Therapeutic efficacy of liposome-encapsulated kanamycin against Mycobacterium intracellulare infection induced in mice. Am Rev Respir Dis, 1991, 144(3 Pt 1): 575-579.
20. Bakker-Woudenberg IA, Lokerse AF, Vink-van den Berg JC, et al. Liposome-encapsulated ampicillin against Listeria monocytogenes in vivo and in vitro. Infection, 1988, 16 Suppl 2: S165-170.
21. Düzgüne? N, Perumal VK, Kesavalu L, et al. Enhanced effect of liposome-encapsulated amikacin on Mycobacterium avium-M. intracellulare complex infection in beige mice. Antimicrob Agents Chemother, 1988, 32(9): 1404-1411.
22. Anderson JC, Kirby CJ. The effect of incorporation of cloxacillin in liposomes on treatment of experimental staphylococcal mastitis in mice. J Vet Pharmacol Ther, 1986, 9(3): 303-309.
23. Bakker-Woudenberg IA, Lokerse AF, Vink-van den Berg JC, et al. Effect of liposome-entrapped ampicillin on survival of Listeria monocytogenes in murine peritoneal macrophages. Antimicrob Agents Chemother, 1986, 30(2): 295-300.
24. Salem II, Düzgüne? N. Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin against Mycobacterium avium complex infection in human macrophages. Int J Pharm, 2003, 250(2): 403-414.
25. Onyeji CO, Nightingale CH, Tessier PR, et al. Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare. J Infect Dis, 1995, 172(3): 810-816.
26. Sou K, Goins B, Oyajobi BO, et al. Bone marrow-targeted liposomal carriers. Expert Opin Drug Deliv, 2011, 8(3): 317-328.
27. Sutherland IW. The biofilm matrix—an immobilised but dynamic environment. Trends Microbiol, 2001, 9(5): 222-227.
28. Kim JH, Gias M, Jones MN. The adsorption of cationic liposomes to Staphylococcus aureus biofilms. Colloids Surf A Physicochem Eng Asp, 1999, 149(1): 561-570．.
29. Tollemar J, Duraj F, Ericzon BG. Liposomal amphotericin B treatment in a 9-month-old liver recipient. Mycoses, 1990, 33(5): 251-252.
30. Katz NM, Pierce PF, Anzeck RA, et al. Liposomal amphotericin B for treatment of pulmonary aspergillosis in a heart transplant patient. J Heart Transplant, 1990, 9(1): 14-17.
31. Halwani M, Yebio B, Suntres ZE, et al. Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. J Antimicrob Chemother, 2008, 62(6): 1291-1297.
32. Offner F, Krcmery V, Boogaerts M, et al. Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B. Antimicrob Agents Chemother, 2004, 48(12): 4808-4812.
33. Abdel-Rhaman MS, Soliman W, Habib F, et al. A New long-acting liposomal topical antifungal formula: human clinical study. Cornea, 2012, 31(2): 126-129.
34. Okusanya OO, Bhavnani SM, Hammel J, et al. Pharmacokinetic and pharmacodynamic evaluation of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infection. Antimicrob Agents Chemother, 2009, 53(9): 3847-3854.
35. 殷凱生, 王彤, 廖萬(wàn)清, 等. 國(guó)產(chǎn)注射用兩性霉素B脂質(zhì)體治療深部真菌病的療效與安全性的臨床研究. 中華醫(yī)學(xué)感染學(xué)雜志, 2004, 14(8): 850-854.
36. Sharma A, Sharma US. Liposomes in drug delivery: progress and limitations. Int J Pharm, 1997, 154(2): 123-140.
37. Mouritsen OG, Jørgensen K. A new look at lipid-membrane structure in relation to drug research. Pharm Res, 1998, 15(10): 1507-1519.
38. Gubernator J, Drulis-Kawa Z, Dorotkiewicz-Jach A, et al. In vitro antimicrobial activity of liposomes containing ciprofloxacin, meropenem and gentamicin against Gram-negative clinical bacterial strains. Lett Drug Des Discov, 2007, 4(4): 297-304.
39. Ulrich AS. Biophysical aspects of using liposomes as delivery vehicles. Biosci Rep, 2002, 22(2): 129-150.
40. Kshirsagar NA, Pandya SK, Kirodian BG, et al. Liposomal drug delivery system from laboratory to clinic. J Postgrad Med, 2005, 51 Suppl 1: S5-15.
41. Kim S, Turker MS, Chi EY, et al. Preparation of multivesicular liposomes. Biochim Biophys Acta, 1983, 728(3): 339-348.
42. Zuidam NJ, Lee SS, Crommelin DJ. Sterilization of liposomes by heat treatment. Pharm Res, 1993, 10(11): 1591-1596.
  1. 1. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipid. J Mol Boil, 1965, 13(1): 238-252.
  2. 2. Gregoriadis G, Wills EJ, Swain CP, et al. Drug-carrier potential of liposomes in cancer chemotherapy. Lancet, 1974, 1(7870): 1313-1316.
  3. 3. 陸彬. 藥劑學(xué). 北京: 中國(guó)醫(yī)藥科技出版社, 2003: 454.
  4. 4. Drulis-Kawa Z, Dorotkiewicz-Jach A. Liposomes as delivery systems for antibiotics. Int J Pharm, 2010, 387(1-2): 187-198.
  5. 5. Shen Y, Ji Y, Xu S, et al. Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: preparation, characterization, and pharmacokinetics. Drug Deliv, 2011, 18(5): 361-366.
  6. 6. Cao J, Sun J, Wang X, et al. N-trimethyl chitosan-coated multivesicular liposomes for oxymatrine oral delivery. Drug Dev Ind Pharm, 2009, 35(11): 1339-1347.
  7. 7. Akiyama M. Slow change in the repeat period of multilamellar dimyristoyl phosphatidylcholine accompanied by thermal phase transition. Biochim Biophys Acta, 1981, 644(1): 89-95.
  8. 8. Bakker-Woudenberg IA. Long-circulating sterically stabilized liposomes as carriers of agents for treatment or for imaging ionfectious foci. Int J Antimicrob Agents, 2002, 19(4): 299-311.
  9. 9. Abeylath SC, Turos E. Drug delivery approaches to overcome bacterial resistence to beta-lactam antibiotics. Expert Opin Drug Deliv, 2008, 5(9): 931-949.
  10. 10. Jia Y, Joly H, Omri A. Liposomes as a carrier for gentamicin delivery: development and evaluation of the physicochemical properties. Int J Pharm, 2008, 359(1-2): 254-263.
  11. 11. Hamidi M, Azadi A, Rafiei P. Pharmacokinetic consequences of pegylattion. Drug Delive, 2006, 13(6): 399-409.
  12. 12. Schiffelers R, Storm G, Bakker-Woudenberg I. Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies. J Antimicrob Chemother, 2001, 48(3): 333-344.
  13. 13. Bakker-Woudenberg IA, Schiffelers RM, Storm G, et al. Long-circulating sterically stabilized liposomes in the treatment of infections. Methods Enzymol, 2005, 391: 228-260.
  14. 14. Beaulac C, Clement-Major S, Hawari J, et al. In vitro kinetics of drug release and pulmonary retention of microencapsulated antibiotic in liposomal formulations in relation to the lipid composition. J Microencapsul, 1997, 14(3): 335-348.
  15. 15. Ceh B, Winterhalter M, Frederik PM, et al. Stealth liposomes: from theory to product. Adv Drug Deliv Rev, 1997, 24(2): 165-177.
  16. 16. Bakker-Woudenberg IA, ten Kate MT, Guo L, et al. Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection. Antimicrob Agents Chemother, 2002, 46(8): 2575-2581.
  17. 17. Bakker-Woudenberg IA, ten Kate MT, Guo L, et al. Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated liposomes for treatment of Klebsiella pneumoniae pneumonia in rats. Antimicrob Agents Chemother, 2011, 45(5): 1487-1492.
  18. 18. Muppidi K, Wang J, Betageri G, et al. PEGylated liposome encapsulation increases the lung tissue concentration of vancomycin. Antimicrob Agents Chemother, 2011, 55(10): 4537-4542.
  19. 19. Tomioka H, Saito H, Sato K, et al. Therapeutic efficacy of liposome-encapsulated kanamycin against Mycobacterium intracellulare infection induced in mice. Am Rev Respir Dis, 1991, 144(3 Pt 1): 575-579.
  20. 20. Bakker-Woudenberg IA, Lokerse AF, Vink-van den Berg JC, et al. Liposome-encapsulated ampicillin against Listeria monocytogenes in vivo and in vitro. Infection, 1988, 16 Suppl 2: S165-170.
  21. 21. Düzgüne? N, Perumal VK, Kesavalu L, et al. Enhanced effect of liposome-encapsulated amikacin on Mycobacterium avium-M. intracellulare complex infection in beige mice. Antimicrob Agents Chemother, 1988, 32(9): 1404-1411.
  22. 22. Anderson JC, Kirby CJ. The effect of incorporation of cloxacillin in liposomes on treatment of experimental staphylococcal mastitis in mice. J Vet Pharmacol Ther, 1986, 9(3): 303-309.
  23. 23. Bakker-Woudenberg IA, Lokerse AF, Vink-van den Berg JC, et al. Effect of liposome-entrapped ampicillin on survival of Listeria monocytogenes in murine peritoneal macrophages. Antimicrob Agents Chemother, 1986, 30(2): 295-300.
  24. 24. Salem II, Düzgüne? N. Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin against Mycobacterium avium complex infection in human macrophages. Int J Pharm, 2003, 250(2): 403-414.
  25. 25. Onyeji CO, Nightingale CH, Tessier PR, et al. Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare. J Infect Dis, 1995, 172(3): 810-816.
  26. 26. Sou K, Goins B, Oyajobi BO, et al. Bone marrow-targeted liposomal carriers. Expert Opin Drug Deliv, 2011, 8(3): 317-328.
  27. 27. Sutherland IW. The biofilm matrix—an immobilised but dynamic environment. Trends Microbiol, 2001, 9(5): 222-227.
  28. 28. Kim JH, Gias M, Jones MN. The adsorption of cationic liposomes to Staphylococcus aureus biofilms. Colloids Surf A Physicochem Eng Asp, 1999, 149(1): 561-570．.
  29. 29. Tollemar J, Duraj F, Ericzon BG. Liposomal amphotericin B treatment in a 9-month-old liver recipient. Mycoses, 1990, 33(5): 251-252.
  30. 30. Katz NM, Pierce PF, Anzeck RA, et al. Liposomal amphotericin B for treatment of pulmonary aspergillosis in a heart transplant patient. J Heart Transplant, 1990, 9(1): 14-17.
  31. 31. Halwani M, Yebio B, Suntres ZE, et al. Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. J Antimicrob Chemother, 2008, 62(6): 1291-1297.
  32. 32. Offner F, Krcmery V, Boogaerts M, et al. Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B. Antimicrob Agents Chemother, 2004, 48(12): 4808-4812.
  33. 33. Abdel-Rhaman MS, Soliman W, Habib F, et al. A New long-acting liposomal topical antifungal formula: human clinical study. Cornea, 2012, 31(2): 126-129.
  34. 34. Okusanya OO, Bhavnani SM, Hammel J, et al. Pharmacokinetic and pharmacodynamic evaluation of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infection. Antimicrob Agents Chemother, 2009, 53(9): 3847-3854.
  35. 35. 殷凱生, 王彤, 廖萬(wàn)清, 等. 國(guó)產(chǎn)注射用兩性霉素B脂質(zhì)體治療深部真菌病的療效與安全性的臨床研究. 中華醫(yī)學(xué)感染學(xué)雜志, 2004, 14(8): 850-854.
  36. 36. Sharma A, Sharma US. Liposomes in drug delivery: progress and limitations. Int J Pharm, 1997, 154(2): 123-140.
  37. 37. Mouritsen OG, Jørgensen K. A new look at lipid-membrane structure in relation to drug research. Pharm Res, 1998, 15(10): 1507-1519.
  38. 38. Gubernator J, Drulis-Kawa Z, Dorotkiewicz-Jach A, et al. In vitro antimicrobial activity of liposomes containing ciprofloxacin, meropenem and gentamicin against Gram-negative clinical bacterial strains. Lett Drug Des Discov, 2007, 4(4): 297-304.
  39. 39. Ulrich AS. Biophysical aspects of using liposomes as delivery vehicles. Biosci Rep, 2002, 22(2): 129-150.
  40. 40. Kshirsagar NA, Pandya SK, Kirodian BG, et al. Liposomal drug delivery system from laboratory to clinic. J Postgrad Med, 2005, 51 Suppl 1: S5-15.
  41. 41. Kim S, Turker MS, Chi EY, et al. Preparation of multivesicular liposomes. Biochim Biophys Acta, 1983, 728(3): 339-348.
  42. 42. Zuidam NJ, Lee SS, Crommelin DJ. Sterilization of liposomes by heat treatment. Pharm Res, 1993, 10(11): 1591-1596.