Lack of understanding of the biological barriers: Drug delivery systems need to overcome several biological barriers, such as the intestinal barrier, the blood-brain barrier, and the tumor barrier, to deliver drugs to the target site. Many non-container-based drug delivery systems fail because they do not adequately address these barriers.

Insufficient drug loading: Non-container-based drug delivery systems have limited drug loading capacity compared to container-based systems, such as liposomes and nanoparticles. This can result in insufficient drug delivery to the target site and reduced therapeutic efficacy.

Poor drug release kinetics: Non-container-based drug delivery systems often have difficulty controlling drug release kinetics. This can lead to rapid drug release, resulting in reduced bioavailability, or slow drug release, which can delay or prevent therapeutic effects.

Off-target effects: Non-container-based drug delivery systems can distribute drugs throughout the body, leading to off-target effects and potential toxicity. For example, if a drug is delivered to a non-target organ, it could cause adverse effects in that organ, limiting the therapeutic potential of the drug.

Lack of biocompatibility: Non-container-based drug delivery systems can be incompatible with the biological environment. This can cause inflammation, immune reactions, and other adverse effects, limiting their use in therapeutic applications.

By overcoming these challenges, it is possible to improve the efficacy, safety, and reliability of non-container-based drug delivery systems. This could lead to the development of novel drug delivery approaches that address unmet medical needs.