PH-responsive tumor-targeted drug delivery
[11] The loading of anti-tumor drugs into pH-responsive polymer nanomaterials can be classified into three categories: chemical bonding, intermolecular force, and physical encapsulation.
When exposed to the low pH, pH-triggered protonation/ionization changes create disturbances of the hydrophilic-hydrophobic balance within the nanocarrier, causing its disassembly and releasing the drug encapsulated within the carrier.
[17] Hydrogels are networks of polymers crosslinked to form a three-dimensional structure capable of absorbing and retaining large amounts of fluids.
With increased capillary action, hydrogels are relatively insoluble unless triggered by the change in pH for tumor-targeted drug carriers.
[18] The physical properties of hydrogels can be adjusted to meet specific requirements for various drug delivery systems.
[12] In the past decade, scientists have been working on engineering an injectable hydrogel post- resection surgery to treat tumor sites.
[19] Polylactide-co-glycolide (PLGA) and polyethylene glycol (PEG) hydrogel is an injectable biomaterial made up of is a copolymer, that has been approved by the Food and Drug Administration (FDA) for use in therapeutic devices due to its biodegradability and biocompatibility properties in the human body.
[20][19] There have been studies done in loading these hydrogels with cancer therapeutic drugs for localized treatment in breast tumors after surgical resection.
pH-responsive liposomes generally consist of weakly acidic amphiphile such as cholesteryl hemisuccinate (CHEMS) and cone-shaped lipids such as Dioleoylphosphatidylethanolamine (DOPE).
[23] DOPE adopts a bilayer structure at neutral pH but forms a hexagonal inverted structure, due to the low hydration of their polar head and neutralization of the negatively charged phosphodiester groups when exposed to acidic conditions, such as tumour sites, leading to destabilization and content release, while remaining stable at physiological pH.
[12] Micelles are typically formed through block polymers self-assembling which can be conjugated with different units, such as polyethylene glycol and poly(amino acid).
However, introducing pH-sensitive chemical bonding arms between polymer chain segments or polymers will allow the micelle to hydrolyze quickly under weakly acidic conditions and work as an efficient drug delivery carrier for pH-responsive tumor-targeted drug delivery.
[10] Some materials that could be used have higher molecular weights, which will not be able to be excreted via the kidneys after releasing the drug at the target area.
[10] Another reason for off-target delivery could be due to the lower pH levels of lesions and inflammation sites.
Studies show that this problem could be overcome by avoiding receptor-mediated active targeting with monoclonal antibodies.
[28] When drug delivery systems tend to have high molecular weight and have a possibility of being toxic to the body due to build-up, companies tend to shy away from taking part in actively testing out these drugs clinically as it can pose a risk for the company in terms of monetary funds as well as ethical issues.
