The present investigation reports a new family of lipid nanoparticles biomimetic of lipoproteins, lipoprotein-mimicking biovectorized systems (LMBVs), for the delivery of methotrexate. LMBVs were prepared by microemulsion congealing technique, and the composition and process were optimized. The palmitoylpolyethylene glycol 4000 (p-PEG 4000) was anchored on LMBVs as apoprotein analogue. Various formulations were prepared and characterized for size and polydispersity, zeta potential, drug entrapment efficiency, anchoring efficiency, release kinetics, pharmacokinetics and tissue distribution. The size was 70-76 nm and the polydispersity was 0.09-0.18. The zeta potential was -63.2 which was reduced to -19.3 after p-PEG 4000 coating. Entrapment efficiency varied from 22.6% to 30.2%. Anchoring efficiency was 74.0 +/- 3.9%. The drug release showed zero-order profile. Their circulation half-life was enhanced and exhibited capability to accumulate in tissues for longer periods. The composition of lipidic part of LMBVs and p-PEG 4000 anchoring impart similarity with natural lipoproteins in terms of in vivo behaviour. This new drug carrier named LMBVs, holds promise for targeting and systemic controlled release, which may prove effective in the treatment of various types of cancer.