Additive-free albumin nanoparticles of alendronate for attenuating inflammation through monocyte inhibition.
OBJECTIVE
Particulated dosage forms of bisphosphonates, such as polymeric nanoparticles and liposomes, deplete circulating monocytes and attenuate inflammation. The aim of this work was to develop a novel formulation of albumin nanoparticles with no crosslinkers that encapsulate the bisphosphonate, alendronate and, further, to examine its bioactivity in vitro and in vivo.


RESULTS
The novel formulation was prepared by desolvation of human serum albumin in acidic pH induced by alendronate, which enables an electrostatic interaction between albumin and the acidic drug. The mean particle size of the negatively charged nanoparticle was 250-300 nm and drug-entrapment efficiency was 49%. The formulation can be filter sterilized and lyophilized for increased stability. Alendronate nanoparticles exhibited significant inhibitory effects on RAW264 macrophage growth and a significant attenuation of stenosis in rats.


CONCLUSIONS
It is concluded that bioactive nanoparticles of human albumin can be formulated without crosslinkers and potentially toxic additives.
Markovsky
Ela
E
The Hebrew University of Jerusalem, Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Jerusalem, Israel.
Koroukhov
Nickolay
N
Golomb
Gershon
G
D000418:Albumins / Q000737:chemistry*; D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D016896:Treatment Outcome
D000418:Albumins; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D019386:Alendronate