Hydroxyethylstarch microcapsules: a preliminary study for tumor immunotherapy application.
The objective of this work was to prepare microcapsules which would allow protection and slow release of antigens used for melanoma immunotherapy treatment. Hydroxyethylstarch (HES) microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride (TC). They were characterized with respect to morphology (microscopy) and size (in the 4-15 microm range). Bovine serum albumin (BSA) was used as model protein for loading and release studies. Microcapsules were loaded with solutions at different protein concentrations (0.5-5%). The maximum loading efficiency (20%) was observed with the concentration of 2.5%, which allowed a loading capacity near 100%. Confocal laser scanning microscopy (CLSM) visualization showed that BSA was entrapped within the microcapsules and not only associated to their outer surface. BSA-release studies showed a 20% BSA release within 30 min while 80% remained entrapped in the microcapsules for 4 days. Microcapsules were degraded by alpha-amylase and addition of esterase to alpha-amylase enhanced slightly their degradation. In vitro studies on melanoma cells showed that HES microcapsules were non-toxic. Preliminary in vivo studies demonstrated that microcapsules were biodegradable after intraperitoneal injection (i.p.). The observation of peritoneal wash showed a complete degradation within 7 days, indicating a possible application as an in vivo drug delivery system especially to enhance the presentation of antigens.
Devy
J
J
Laboratoire de Pharmacotechnie, FRE CNRS 2715, IFR53, Faculté de Pharmacie, 51096 Reims Cedex, France.
Balasse
E
E
Kaplan
H
H
Madoulet
C
C
Andry
M-C
MC
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000627:therapeutic use; D001673:Biodegradation, Environmental; D002214:Capsules; D002470:Cell Survival; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004950:Esterases; D005260:Female; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D007274:Injections, Intraperitoneal; D008546:Melanoma, Experimental; D051379:Mice; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D000516:alpha-Amylases
D000941:Antigens; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006895:Hydroxyethyl Starch Derivatives; D012710:Serum Albumin, Bovine; D004950:Esterases; D000516:alpha-Amylases