||A novel polymeric nanoparticle was prepared to effectively deliver insoluble amphotericin B (AmB), because it is poor in bioavailability and is a serious concern for the treatment of fungal infections due to nephrotoxicity, high insolubility and toxicity. The use of drug delivery systems can improve the bioavailability of these antifungal drugs. Poly(Ethylene glycol)(PEG) was conjugated to improve solubility of AmB, and that was grafted to O-carboxymethyl chitosan (OCMCh) with disulfide bond. In addition, to provide fungal-targeting ability in blood stream or into infected tissues, an antifungal peptide, histatin 5, was conjugated to carboxyl groups of OCMCh(HOSP-AmB). The nanoparticles were characterized FT-IR, H-NMR, DLS and HPLC. Interestingly, HOSP-AmB showed more potent antifungal activity than free-AmB and histatin 5-free nanoparicle(OSP-AmB) in vitro and in vivo, indicating that histatin 5 contributes targeting and synergetic effects. In addition, the releasing pattern of AmB from HOSP-AmB nanoparticle was detected by using small-angle neutron scattering(SANS).