TABLE I.

Examples of combinatorial libraries of NPs.

Year	Library size	Method	Chemistry	Selected references
Cationic polymers and oligomers
	First generation libraries		Michael-type addition (conjugation addition of primary or secondary amines to diacrylates)
2001	140 polymers	Low throughput		23 and 24
2003	2350 polymers	Semi-automated		69
2003	24 polymers	HTS		47
	Second generation libraries:
2005	>500 polymers	HTS		48–50
2005	486 polymers	HTS (reduction to milligrams scale of the original library)		51–54
2007	Third generation libraries:			55, 81, and 104
	Photopolymerized	HTS (polymeric microarrays with robotic fluid handling)	Michael-type addition, followed by polymerization of amines and acrylates with a light-activated radical initiator
2004	576 polymers			112
2005	1152 polymers			113
2005	1700 polymers			114
2006	120 polymers			27
	Terpolymers	HTS	Polymerization of diacrylates, a hydrophobic alkylamines and hydrophilic amines Ring opening polymerization and Michael step‐growth polymerization
2013	80 terpolymers			87
2016	6 terpolymers			88
2018	16 terpolymers			89
Lipid-polymer hybrids
2014	500 NPs	HTS	Epoxide ring-opening reaction (conjugation of epoxide-terminated lipids to low MW polyamines)	115
	Extended work
	Polymer 7C1			57–59
Lipid-like nanoparticles
	First generation libraries:	HTS	Michael-type addition Epoxide ring-opening reaction (by amine substrates)
2008	1200 NPs (pilot library: 700 NPs)			28, 30, and 31
2010	126 NPs			56, 60, and 61
	Second generation libraries:	HTS	Michael-type addition One-pot synthesis (thiolactone ring opening)
2010	51 NPs			73
2011	3780 NPs			74
2012	54 NPs			29
2013	32 LNPs			116
2014	1400 NPs			43
2018	288 NPs			67 and 102
	Microfluidics	HTS
2012	70 NPs			117
2020	14 NPs			90