Oral administration of nutrient/drug is the most common and preferred route. However, a number of barriers are encountered
after ingestion, limiting efficient oral nutrient/drug absorption. Both lipid-based (e.g., nanoemulsion, solid lipid nanoparticles) and
polymer-based (e.g., protein and polysaccharide nanoparticles) nanoscale delivery systems have demonstrated capability to overcome
some of these physiological barriers during transportation and metabolism stages. To better deal with those barriers, polymer-lipid
complex nanoparticles are being explored and developed to merge the beneficial features and overcome the respective
shortcomings of lipid-based and polymer-based nanoparticles. This paper aims to provide an overview of the various preparation
strategies and supramolecular interactions of orally administered polymer-lipid complex nanoparticles by reviewing recent studies.
Two types of polymer-lipid complex nanoparticles have been developed, i.e., lipid core with polymer shell nanoparticles and
polymer core with lipid shell nanoparticles (lipid-polymer hybrid nanoparticles). Besides, both natural and synthetic polymers used
for fabrication are discussed and their advantages and disadvantages are highlighted. Further research work is needed to optimize
the fabrication and scaling up processes, so that these versatile polymer-lipid complex nanoparticles could have a significant impact
on the oral delivery of nutrient/drug.