Aspects

pH-sensitive nanoparticles

Ref.

Premature Drug Release

One of the main issues with pH-sensitive nanoparticles is the risk of unintended drug release caused by variations in the body's pH levels. This premature release can diminish the drug's effectiveness and negatively impact the overall success of the treatment.

[58]

Stability Issues

One challenge with pH-sensitive nanoparticles is their potential instability in specific physiological conditions. Fluctuating pH levels across various tissues may trigger inconsistent drug release, making it difficult to achieve reliable therapeutic effects.

[59]

Biocompatibility Issues

Nanoparticles are often internalized by cells based on factors like size and surface charge. This can lead to cytotoxicity if not carefully designed.

Nanomaterials may accumulate in organs such as the liver, spleen, and lungs. This accumulation can be advantageous for targeting specific tissues but also poses risks of organ-specific toxicity.

[60, 61]

Toxicity Issues

Nanomaterials can induce the production of reactive oxygen species (ROS) when they come into contact with biological systems. ROS are highly reactive molecules that can cause oxidative stress, which leads to the damage of cellular components such as lipids, proteins, and DNA. This oxidative damage can contribute to cell death and tissue damage.

Nanomaterials may accumulate in certain organs like the liver, lungs, kidneys, and spleen, depending on their characteristics and how they are administered. This targeted organ toxicity raises significant concerns, as the buildup of nanomaterials in non-intended organs may cause hepatotoxicity, nephrotoxicity lung damage, especially if the body's ability to eliminate these materials is ineffective.

[62, 63]

Synthetic pH-sensitive polymers

Synthetic hydrogels, including polyacrylamide and polyethylene glycols-based hydrogels, may produce toxicity risks due to the presence of residual monomers, crosslinking agents, and degradation by-products. These substances have the potential to cause cytotoxic effects, inflammation, or immune system reactions. Additionally, some synthetic hydrogels may lead to localized irritation, particularly when used in long-term medical implants, as slow or incomplete degradation can result in harmful accumulation within tissues

Synthetic polymers like PAA and poly (methacrylic acid) offer the advantage of enhanced drug stability and controlled release.

[64, 65]

Natural pH-sensitive polymers

Natural hydrogels, such as alginate and hyaluronic acid, demonstrate excellent biocompatibility due to their structural similarity to the body's extracellular matrix. This makes them highly suitable for wound healing, tissue regeneration, and drug delivery.

Chitosan and alginate are widely recognized for their exceptional biocompatibility and low toxicity, making them highly suitable for drug delivery applications.

[64, 65]