Nanotechnology advancements have enabled the design of drugs that can be absorbed or bonded on the surface of nanoparticles, encapsulated in the core, or dissolved inside the particle matrix, allowing for the introduction of targeted, safe, i.e., effective nanoparticle (NP) drug formulations. Nanodrug delivery methods have the ability to improve hydrophobic drug solubility, enhance drug biodistribution and pharmacokinetics, and provide preferential accumulation at the target site.
Currently, common drug nanocarriers are classified as lipid-based nanoparticles, polymer nanoparticles, and inorganic nanoparticles. Because of their physicochemical properties such as simple formulation, good biocompatibility, high bioavailability, and high payload, lipid-based nanoparticles (LNPs) are the most common types of FDA-approved nanomedicines, and liposomes are the most common and well-studied nanocarriers among them. Polymeric nanocarriers, on the other hand, are a relatively novel technique that is regarded as suitable drug delivery materials due to physicochemical qualities such as biodegradability, biocompatibility, water solubility, and storage stability.
Polymers are divided into linear polymers, dendrimer polymers, and hyperbranched polymers (HBPs) based on their structure. Different polymer structures are used in drug delivery systems diversely based on their respective advantages, such as encapsulating the drug in a reservoir within a polymer coating (reservoir type), embedding the drug in a polymer matrix (monolithic type), carrying the drug via polymer-drug conjugation, and introducing targeting factors to load the drug to a specific disease site.
Polymeric micelles: Liposome-like structure
The drug is stored and delivered in the form of a polymer package (drug reservoir enclosed in a polymeric coating) in a reservoir-based polymeric nano-delivery system, which transports the drug to the target location and controls the drug's release via the polymer's physicochemical properties, such as active or passive targeting.
Unlike the reservoir type, in the monolithic polymeric drug delivery system, the drug is dissolved or dispersed in the polymer matrix and becomes integral with the delivery vehicle. There are also similarities in that the drug mixed with the polymer will be contained or encapsulated within the polymer. Linear polymers are often used as drug carriers or surface coatings for nanoparticles to improve biocompatibility or solubility and prolong in vivo circulation time. Among them, polyethylene glycol (PEG) is one of the most widely used polymers, followed by hydrolyzed polymaleic anhydride (HPMA). Polymer-modified drugs such as linear PEG and HPMA have now entered clinical trials.
Polymeric micelles, which are generated by amphiphilic block copolymers with both hydrophilic and hydrophobic groups, are a practical application of this type of polymeric carrier. Polymeric micelles are being frequently employed for medication delivery, particularly in oncology.
Dendritic macromolecules: precise and controllable physicochemical properties
Whereas in polymer-drug conjugation systems, drugs are conjugated with polymers and delivered as covalent conjugates with water-soluble and biodegradable polymers. Dendrimers are mainly used in drug-drug conjugation in the direction of drug delivery.
Dendrimers are a type of synthetic polymeric material with a well-defined three-dimensional structure made up of three basic units: core, extra-core repeating units, and surface functional groups, the mass, size, shape, and surface chemistry of which may be precisely regulated. Some common dendrimers include polypropyleneimines, polyamidoamine (PAMAM) dendrimers, etc.
The highly branched, symmetrical, and radial properties of dendrimers allow the active functional groups on the outside of the dendrimer to couple biomolecules or contrast agents to the surface and for drugs to be loaded inside them. As a result, dendrimers are capable of loading many types and larger amounts of drugs and can enhance the solubility of insoluble drugs, which are most commonly studied at this stage for the delivery of nucleic acids and small molecules.
Although polymers have lots of advantages for drug delivery, they do have some limitations, such as low drug concentration at the target location, a lack of defined targeting, and poor in vivo safety, which must be addressed further.
