Table 2.

Summary of studies using block copolymers as a treatment in DMD models in vivo

Copolymer	Pathophysiology	DMD model	Treatment time	Dosage	Delivery route	Results	References
P188	Cardiomyopathy	mdx	Pre-treatment (30 min)	460 mg/kg	i.v.	P188 significantly improved cardiac hemodynamic response and animal survival during cardiac stress testing	Yasuda et al. (2005) [80]
P188	Skeletal muscle	mdx	Pre-treatment (30 min)	600–1800 mg/kg	i.p.	No significant difference in % EBD penetration in rectus femoris muscle fibers in P188 treated mdx mice exercised by downhill treadmill running	Quinlan et al. (2006) [150]
P188	Cardiomyopathy	GRMD	8 weeks	60 mg/kg/hr	i.v.	Chronic P188 treatment normalized serum cTnI levels, blocked increases in heart failure marker BNP, significantly decreased cardiac fibrosis, and prevented dilated cardiomyopathy. Cardiac hemodynamic function in response to dobutamine stress was significantly improved compared to saline treatment. Serum CK levels were not affected.	Townsend et al. (2010) [148]
P188	Cardiomyopathy	mdx	2–4 weeks	460 mg/kg	i.p.	P188 treatment prevented a decrease in cardiac function in response to isoproterenol stress testing. Treated mice did not show significant differences in cardiac fibrosis but had increase in EBD positive fibers, these hearts showed increased systolic function compared to untreated hearts.	Spurney et al. (2010) [149]
P188	Skeletal muscle	mdx	Pre-treatment 2-week daily	30 mg/kg, 460 mg/kg	i.p.	Single dose P188 treatment induced an increase in specific force and decreased the number of IgG positive fibers in both non-stressed and stressed muscles. P188 treatment improved the histological appearance in TA muscles under some conditions. 2-week P188 did not affect TA force. During lengthening contraction injury, it was reported that in a subset of contractions the P188 treatment group had slightly but statistically significant lower force than saline control.	Terry et al. (2014) [151]
P188, P338	Skeletal muscle	mdx	Pre-treatment (0.5–3 h)	60–460 mg/kg	i.p., i.v., s.c., i.m.	Subcutaneous but not intravenous nor intraperitoneal injection of P188 significantly decreased the force loss during and after lengthening contractions of hindlimb mdx muscle and significantly decreased EBD uptake into TA myofibers post-injury. Subcutaneous delivery of PEO8000 had no protective effect. Lower dosage of intraperitoneal and intramuscular but not subcutaneous or intravenous injections of P338 shows significant protective effect.	Houang et al.(2015) [156]
P188	Respiratory	mdx	Q.D., 22 weeks	3 mg/kg	s.c.	Chronic delivery of P188 had significant positive effects on respiratory function parameters and improved diaphragm histological parameters and caused improvement in cardiac hemodynamics of treated mdx mice	Markham et al. (2015) [217]
	Cardiomyopathy	mdx/utr −/−	Q.D., 8 weeks	1 mg/kg	s.c.	P188 treatment slowed the loss of respiratory function and improved diaphragm histological parameters in double knockout mice
diP188 diP188-CH3 diP188-(CH3)3	Skeletal muscle	mdx	Pre-treatment (0.5–3 h)	1000 mg/kg	i.p.	A diblock copolymer architecture confers membrane stabilization. The addition of a single hydrophobic tert-butoxy end-group to the PPO core significantly enhanced membrane protection against lengthening contractions. The less hydrophobic methoxy and hydrophilic hydroxyl end groups did not confer membrane protection in vivo.	Houang et al.(2017) [183]

i.v., intravenous; i.p., intraperitoneal; s.c., subcutaneous; i.m., intramuscular; EBD, Evans blue dye; GRMD, golden retriever muscular dystrophy; cTnI, cardiac troponin I; BNP, brain natriuretic peptide; CK, creatine kinase; TA, tibialis anterior; Q.D., daily; diP188, diblock P188