Table 1.
Comparison of polymer subtypes and modifications.
| Polymer Type | Common Synthesis Techniques | Advantages | Disadvantages | Specific Uses Cited |
|---|---|---|---|---|
| Polyanhydride | Most often via polycondensations from diacids or diacyl anhydrides; can also be prepared via solvent evaporation from emulsion, or thiol-ene ‘click’ polymerization, or melt condensation; NP synthesis via nanoprecipitation | Well-characterized; biocompatible; biodegradable; modifiable (depending on copolymer and surface ligand composition); hydrophobic; predictable rate of release/erosion | Rapid erosion can lead to inadequate ligand retention times; difficult to synthesize; limited stability of loaded peptides and proteins due to nucleophile acylation | Gliadel® (BCNU) wafer for local, sustained-release chemotherapy [14]; drug delivery across the BBB [21]; delivery of non-proteinaceous cargo [16] |
| Poly (lactic-co-glycolic acid) | Co-polymerization of cyclic dimers of glycolic acid and lactic acid; NP synthesis via emulsification-evaporation, nanoprecipitation, phase-inversion, and solvent diffusion; emulsification-evaporation and nanoprecipitation are most commonly used when loading hydrophobic moieties | Widely used; biocompatible; simple biodegradability; easily synthesized; modifiable charge, hydrophobicity, and degradation rate; sustained drug-release; good BBB/tumor penetration | Poor drug loading efficiency; poor drug target delivery efficiency due to high burst release; destabilization of acid-sensitive drugs/peptides | Encapsulation of chemotherapeutics with toxicity profiles indicating sustained, low dosing [7]; microsphere and microparticle drug delivery systems [23] |
| Poly (β-amino ester) | Conjugate addition of amines to bis(acrylamides) and copolymerization; NP synthesis via solvent/anti-solvent formulation | Established safety profile; biocompatible; biodegradable; easily synthesized; high efficacy; pH buffering capacity; able to escape endosomes and allow intracellular expression of nucleic acids | Instability in blood (rapid hydrolysis) without surface modifications; limited ability to achieve widespread gene transfer due to adhesive interactions with ECM | Delivery of polynucleotides and other acid-labile compounds [36]; delivery of nucleic acids to cells [44] |
| Chitosan | Enzymatic or chemical deacetylation of chitin, usually through hydrolysis, produces chitosan; NP synthesis via emulsification and crosslinking, microemulsion, precipitation, or ionic gelation | Biodegradable; capable of mucous membrane adherence and transcytosis; sustained drug release; putative preferential release in tumor acidic environment | Low solubility at physiological pH; tendency to aggregate | Nose-to-brain delivery (via mucous membrane adherence) [46]; in situ gelation [73]; tumor targeting via differential pH [47] |
| Poly(amidoamine) dendrimers | Convergent (beginning with exterior and adding end groups while working towards the core) or divergent synthesis (beginning with core and adding end groups towards the exterior); end group additions via conjugate addition | Biocompatible; flexible, non-toxic; stable; highly soluble; small; modifiable; large hydrophilic surface area; presence of cavities; resistance to denaturation after freezing/thawing | Associated with (modifiable) cytotoxicity; synthesis can lead to heterogeneous mixture of dendrimers unless additional purification steps are completed | Precision-targeting [52]; delivery across the BBB [54]; encapsulating particularly insoluble contents [53] |
| Poly(caprolactone) | Polycondensation of 6-hydroxyhexanoic acid, or ring-opening polymerization of ε-caprolactone; NP synthesis via nanoemulsification, supercritical fluid extraction of emulsion, or solvent evaporation | Biodegradable; non-toxic; modifiable; stable | High hydrophobicity (slow degradation rate of months/years) | Combination with other copolymers to tailor NP suitability to cargo [56] |
| Poly(alkyl cyanoacrylate) | Free radical, anionic, and zwitterionic polymerization; NP synthesis via polymerization in aqueous acidic phase or through interfacial emulsion polymerization | Biodegradable; modifiable; enhanced intracellular penetration; capable of overcoming multidrug resistance | BBB translocation ability remains controversial | Hydrogel-incorporated drug delivery [66]; delivery of nucleic acids and peptides [66]; continuous drug delivery (vs. bursts) [66]; instances of multidrug resistance [70] |
| Polymer Modification | Advantages | Disadvantages | General Uses | |
| Polyethylene glycol | Widely used; classified as GRAS; increases systemic circulation time of NPs; reduces recognition of NPs by immune cells; decreases NP aggregation, opsonization, and phagocytosis | Reduced cellular uptake of PEGylated NPs | Modify NP to reduce immunogenicity | |
| pH | Can improve selective tumor targeting via triggered drug release | Limits the types of cargo able to be carried within the NP | Modify NP to selectively target tumor tissue and spare surrounding parenchyma | |
| Size | Can increase NP stability; can potentially increase BBB/BBTB penetration and brain parenchymal spread | Conflicting in vitro/in vivo results on ideal size of NPs for BBB/BBTB penetrance, brain tissue spread, and cellular uptake | Modify NP to increase intra-tumoral spread | |
| Shape | Can modulate NP circulation time, cellular uptake, and BBB penetration | Certain shapes promote accumulation in non-target organs; ideal shape, depending on delivery mechanism, requires further investigation | Modify NP to maximize efficacy based on delivery mechanism (e.g., nose-to-brain vs. across BBB) |