Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles

• Published in: Biomaterials Vol. 31; no. 13; pp. 3657 - 3666
• Main Authors: He, Chunbai, Hu, Yiping, Yin, Lichen, Tang, Cui, Yin, Chunhua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2010
• Subjects: Advanced Basic Science; Animals; Biodistribution; Cell Line; Cellular uptake; Dentistry; Fluorescence labeling; Humans; Macrophages - metabolism; Mice; Nanoparticles; Neoplasms, Experimental; Particle Size; Polymeric nanoparticles; Polymers - pharmacokinetics; Surface charge; Surface Properties; Tissue Distribution; Chitosan hydrochloride; Camptothecin; Particle size; APS; CPT; FITC labeled protamine sulfate; RhB-CHNP; Carboxymethyl chitosan; CPT loaded RhB-CHNP; Biodistribution; CMCNP; RhB-CMCNP-PS; Nanoparticles; Cellular uptake; Ammonium persulfate; Chitosan hydrochloride grafted nanoparticles; FITC-PS loaded RhB-CMCNP; CMC; Carboxymethyl chitosan grafted nanoparticles; MMA; Surface charge; CH; RhB-CMCNP; RhB; RhB-CHNP-CPT; NPs; Polymeric nanoparticles; RhB labeled CHNP; Fluorescence labeling; CHNP; FITC-PS; Rhodamine B; Methyl methacrylate; RhB labeled CMCNP
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.01.065

Abstract To elucidate the effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles (NPs), rhodamine B (RhB) labeled carboxymethyl chitosan grafted NPs (RhB-CMCNP) and chitosan hydrochloride grafted NPs (RhB-CHNP) were developed as the model negatively and positively charged polymeric NPs, respectively. These NPs owned well defined particle sizes (150–500 nm) and Zeta potentials (−40 mV – +35 mV). FITC labeled protamine sulfate (FITC-PS) loaded RhB-CMCNP and camptothecin (CPT) loaded RhB-CHNP with high encapsulation efficiency were prepared. The fluorescence stability in plasma and towards I− was investigated, and the result indicated it was sufficient for qualitative and quantitative analysis. NPs with high surface charge and large particle size were phagocytized more efficiently by murine macrophage. Slight particle size and surface charge differences and different cell lines had significant implications in the cellular uptake of NPs, and various mechanisms were involved in the uptake process. In vivo biodistribution suggested that NPs with slight negative charges and particle size of 150 nm were tended to accumulate in tumor more efficiently. These results could serve as a guideline in the rational design of drug nanocarriers with maximized therapeutic efficacy and predictable in vivo properties, in which the control of particle size and surface charge was of significance.