The inherent toxicity of nanoparticles, also shown at exceeded dosage / unwanted bioaccumulation, interactive outcomes inhibiting the desired action, loss or misdirected portions of the nanomaterials at other sites in a targeted delivery regime, are some of the associated risks which need be pre-evaluated for better outcomes.
Disadvantageous are not specific. Typically there are many which can be apply for any specific drug. When the size is reduced stability of dosage form falls. Cytotoxicity is a major issue. Usually, we do not evaluate the environmental impact. This is a booming area which must get enough concern due to bio accumulation and many unseen impacts. Sri Lankan scientists and researchers are addressing this now.
One of them could be the physical stability especially when the nanoparticles are in a liquid form and stored at room temperature. The mean size will increase and will produce a bimodal of PDI.
you can also consider physiological insolubility in body serum, unstability in theirs formulation, innate toxicity of nanoparticles, and theirs specific accumulation as disadvantages of targeted drug delivery.