Stabilized Polymer Micelles for the Development of IT-147, an Epothilone D Drug-Loaded Formulation

Table 1

Physiochemical characterization of epothilone D pilot formulations with iron-hydroxamate or disulfide bond stabilization. Formulations were performed with each polymer listed as an entry number and characterized by drug weight loading, efficiency, particle size, and dialysis above and below the critical micelle concentration. Entry numbers 1 and 7 represent the leads selected for screening, and entry number 2 represents the scaled-up lead formulation.

Entry number	Polymer core block	Polymer stabilizing block	Weight loading (% w/w)	Efficiency (%)	Average diameter (nm)	Dialysis > CMC (% remaining)	Dialysis < CMC (% remaining)
1	D-/; L-/; D-	NHOH	3.4	66	70	90	60
2	D-/; L-/; D-	NHOH	4.4	91	75	94	68
3	D-/; L-	NHOH	3.3	64	70	80	25
4	D-/; L-/; D-	NHOH	3.0	58	91	91	28
5	D-/; L-/; D-Asp5	NHOH	1.7	33	97	82	28
6	D-/; L-/; D-	NHOH	0.9	17	>200	55	<10
7	L-/; D-	Cysteine	3.7	72	68	94	38
8	D-/; L-	Cysteine	2.9	56	86	87	11
9	D-/; L-	Cysteine	0.1	<1	35	ND	ND
10	L-/; D-	Cysteine	0.1	<1	>200	47	<10
11	D-/; L-/; D-	Cysteine	0.5	1	>200	ND	ND