8.5.3.2 Factors affecting the selection of host ma...
The selection of host materials used in polymer MNs should consider the following factors in addition to biological safety and stability.
1.Mechanical strengths
The mechanical strengths of the MNs are determined by the wall thickness，wall corner，tip radius，length，distance between the needles and polymer composition of the MNs，so different categories of polymers differ in mechanical strengths.The carried drugs and NPs also pose effects to the mechanical strengths of the MNs.For example，in one of our research，when 368μgphotosensitizer ALA was loaded into the hyaluronic acid MNs，the Young's moduli of the MNs decreased from 58.9 MPa to 40.0 MPa.While in another research，4 μg AuNC was loaded into hyaluronic acid MNs and the Young's moduli of the MNs increased from 68.9 MPa to 224.9 MPa.
2.Solubility/swelling ability of host materials
The solubility or swelling ability of the MNs is of importance to drug release rate.When designing a MN，the host material needs to be tailored to the drug release requirements.In the treatment of some skin diseases，the rapid release of drugs is required to quickly reach the effective local concentration or blood concentration，such as chemotherapy drugs，photosensitizers，photothermal agents，analgesic drugs，and anti-itch drugs.While in inflammatory diseases management，such as psoriasis and eczema，it is proper for long-term slow release of drugs.In addition，in the immunotherapy of skin diseases，it is necessary to consider the time course of the immune events and the specific mechanism of drugs to determine the time and speed of drug release.Of note，even for the treatment of the same disease，the requirement for drug release is also different due to the diverse nature of drugs.For example，antibiotics are classified into“concentration-dependent”and“time-dependent”.When treating skin infections，the former needs to release drugs quickly to reach the effective drug concentration，while the latter needs to release drugs relatively slowly to ensure the action time with effective drug concentration.Water-soluble polysaccharides and their analogues，such as hyaluronic acid（HA），poly（vinyl pyrrolidone）（PVP），dextran，hydroxypropyl methyl cellulose（HPMC），hydroxypropyl cellulose（HPC），carboxymethyl cellulose（CMC）and amylopectin can be quickly and completely dissolved，so they are often used to prepare MNs that require rapid drug release.Conversely，poly（lactic acid）（PLA），poly（lactic-co-glycolic acid）（PLGA），polycarbonate（PC），poly（glycolic acid）（PGA），polycaprolactone（PCL），chitosan and silk are insoluble in water but can be slowly degraded in the body，which are often used to prepare MNs that need to be slowly released.The swelling property of the polymers is another important mechanism for the continuous administration.The swellable MNs made of swellable polymers can absorb a large amount of water without dissolving，and its diffusion is determined by the swelling ability and crosslinked structure of the drug molecules and polymers.Common swellable polymers include poly（hydroxyethyl methacrylate）（PHEMA），polystyrene-block-poly（acrylic acid）（PS-b-PAA），poly（vinyl alcohol）（PVA），poly（methyl vinyl ether-maleic acid）（PMVE/MA，Gantrez），hyaluronic acid acrylate，etc.(https://www.daowen.com)
3.Targeting ability
Some polymer materials have natural targeting properties（e.g.，HA can selectively bind to the CD44 receptor of cancer cells）.Besides，other polymers can target specific cells and/or tissues through redox reactions.
4.Responsive release
Polymer MNs can be designed to respond to specific environments or specific signals.Common response-evoked signals include specific pH，blood glucose concentration，hypoxia，temperature，light，mechanical force，and enzymes or receptors.Swellable MNs based on anionic and cationic polymers exhibit pH-sensitive swelling property and responsive release capabilities.For example，the cationic polymer PEG-b-poly（β-amino ester）releases the drug 4 times faster in a slightly acidic environment（pH is 6.5-7.0）than that in the environment with pH=7.4.McCoy et al.prepared photoresponsive swellable MNs by cross-linking poly（2-hydroxyethyl methacrylate）（PHEMA）and ethylene glycol dimethacrylate，which obtained a long-term release（up to 160 h）of light-responsive drug.Some polymers swell highly at low temperature，but shrink when the temperature rises to a certain value.For example，poly（methoxydiethylene glycol methacrylate）（PmDEGMA）and poly（methoxytriethylene glycol methacrylate）（PmTEGMA）show heat-responsive drug release.When the temperature is above the critical temperature，the drug molecules are squeezed out of the contracted gel and released.Importantly，polymer MNs can be combined with NPs with controlled release and targeting functions，which is highly promising in TDD（see extended reading 3）.