TABLE 1.

Nanoformulations for brain drug delivery of small HH inhibitors. Table shows composition, in vitro and in vivo efficacy, size, and the BBB crossing ability of the nanoparticles for SHH-MB treatment under investigation.

Free drug	Target	NPs	DDS	In vitro Efficacy	In vivo Efficacy	Size (nm)	NP BBB crossing ability	Ref.
Sonidegib (LDE225)	SMO	eHNP-A1-CD15 (DMPC, ApoA1, anti-CD15)	Liposomal nanoparticles	Cell viability inhibition DAOY; PZp53	HH-dependent MB growth inhibition and extended survival in SmoA1; Math-Cre-ER-Ptchflox/flox mice	28	Detected in brain (24 h post i.v.)	Kim et al. (2020)
Vismodegib (GDC-0449)	SMO	POx (polyoxazoline block copolymer)	Polymeric micelles	—	Reduction of free-drug systemic toxicity and extended survival in Healthy mice; Gfap-Cre/SmoM2 100 mg/kg	25–40	Not able	Hwang et al. (2020)
HPI-1	GLI1	NanoHHI (PLGA-PEG)	Polymer nanoparticles	—	HH-dependent MB growth inhibition in allograft model of primary MB cells from SmoWT/SmoD477G; Ptch+/−; Trp53−/− mice 30 mg/kg	100	Detected in brain (3.9±2.1 mg/g 10’ post i.v.; 1.4 ± 0.4 mg/g 30’ post i.v.)	Chenna et al. (2012)
GlaB	GLI1	mPEG5kDa-cholane	Polymeric micelles	Cell viability inhibition in primary MB cells from Math1-Cre/PtcC/C mice	HH-dependent MB growth inhibition and extended survival in allograft model of primary MB cells from Math1-Cre/PtcC/C mice 9 mg/kg	21.7 ± 0.7	Detected: in brain (1.93% ID/g 1 h post i.v.; 1.8% ID/g 2 h post i.v.) in cerebellum (1.87% ID/g 1 h post i.v.; 1.67% ID/g 2 h post i.v.)	Infante et al. (2021)

NPs, nanoparticles; DDS, drug delivery system; n.a., not available.