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Macromolecular drugs, especially peptide drugs, are taking a stably increasing percentage in global pharmaceutical market.However, since most of them should be applied repeatedly in a therapy, these drugs are commonly administrated by frequent injection due to their vulnerability of enzymolysis or hydrolysis in the gastrointestinal tract, which will in turn lead to poor compliance of patients.Several novel administration routes have been well studied to find a way out.It is worth mentioning that there are three mature drug delivery systems proving new insights: long-acting injection microspheres, pressurized metered-dose inhalers (pMDIs) and microneedles.More specifically, injection frequency can be drastically reduced by utilizing long-acting injection microspheres technologies;self-administration and painless application are capable in pMDIs and microneedles.Microspheres for long-acting injection, typically with diameters in the micrometer range,are prepared via emulsification evaporation, phase separation and spray drying in laboratory.Regrettably, the use of surfactant, organic solvent or other additives may cause the inactivation of peptides and unsatisfactory reproducibility.With the aim to construct a bridge to connect laboratory investigation and industrial production, Ultra-fine particle process system (UPPS) was developed.Microspheres were prepared by UPPS using with a wide range of drugs and polymers and without addition of surfactant or organic solvent.All the relevant studies revealed that UPPS was able to provide optimal reproducibility in a quick and simple process.Amongst the notable approaches of macromolecular drugs delivery, pulmonary drug delivery system (PDDS) is a highly promising one.In order to overcome the critical issue, i.e.,inactivation of peptide drugs during preparation and storage, bottom-up preparation process was employed to establish solid nanoparticle and microemulsion systems, which were subsequently added propellant to produce pressurized metered-dose inhalers (pMDIs).Peptide drugs showed uniform particle size and suspended homogeneously in the propellant,free from inactivation in both systems, and the pMDIs exhibited satisfactory in vitro aerosol particle size distribution and in vivo pharmacologic effect.It has been well documented that microneedles are able to improve the bioavailability of peptide drugs.The development of peptide containing dissolving microneedle array (DMNA) has been focused on by our groups.It was illustrated that the DMNA loaded with appropriate proportion of peptide drugs possessed favorable mechanical strength and delivery efficiency.Long-acting injection microspheres, pMDIs and microneedles all have unique advantages in macromolecular drugs delivery.After further development, they can be more popular and relieve the pain of patients.