Table 1.

Sensitivity analysis of inhaled RIF model parameters at different dose frequencies on treatment related model outputs^a

		Carrier release parameters					Mϕ targeting parameters							PK parameters
	Rifampicin	Pload	Psize	PdrugDiff	PintDeg	PextDeg	Pzeta	Pdiff	Muptake	PTL	MTR	KD-TLR	kTLR	kabs	CLabs	Vp	CLp
Daily	CFU	−−−	+	−−−	−												+
	Lesion AUC	+++	−−	+++	+++	+++	++	−	−−−		−						−−−
	Peripheral AUC	+++	−−−	+++	+++	+++										+++	−−−
	Time to sterilization	−−−		−−											−		+
2 weeks	CFU	−−−			+	+++											+
	Lesion AUC	+++		+++	++	+	+		−		+						−−−
	Peripheral AUC	+++		+		+				−						+++	−−−
	Time to sterilization	−−−

P_load, load mass of drug (mg/carrier); P_size, size of carrier (μm); P_drugDiff, diffusivity of drug in carrier (μm²/s); P_intDeg, carrier intracellular degradation rate (L/s); P_extDeg, carrier extracellular degradation rate (L/s); P_zeta, carrier zeta-potential (mV); P_diff, diffusivity of carrier in lung tissue (cm²/s); M_uptake, macrophage maximum carrier uptake probability (unitless); P_TL, carrier density of targeting ligand (#/carrier); M_TR, macrophage density of targeting receptor (#/cell); K_D-TLR, ligand-receptor dissociation constant (M); k_TLR, ligand-receptor carrier uptake rate (#/cell^*s); k_abs, absorption rate constant (1/hr); CL_abs, clearance rate from the second absorption compartment (L/h^*kg); V_p, peripheral volume distribution (L/kg); CL_p, clearance rate from peripheral compartment (L/h^*kg); -/+, P < 0.05; --/++, P < 0.001; ---/+++, P < 0.0001 from sensitivity analysis.

^aCarrier dose used: 1.2×10⁹ carriers. +/- signs indicate positive or negative correlations. The number of +/- signs indicates the strength of correlations (e.g., +++ vs. + indicates a stronger positive correlation of the former parameter compared to the latter parameter).43