Preparation of novel biodegradable ropivacaine microspheres and evaluation of their efficacy in sciatic nerve block in mice

Figures & data

Figure 1 Structure of (A) bupivacaine and (B) ropivacaine.

Figure 2 The morphology of the RPC-loaded chitosan microspheres observed by SEM.

Abbreviations: RPC, ropivacaine; SEM, scanning electron microscopy.

Figure 3 The release profiles of free RPC (◊, jade line) and RPC-loaded chitosan microspheres (Δ, purple line) (n=3).

Note: Each point represents the mean ± standard deviation.
Abbreviation: RPC, ropivacaine.

Table 1 Release kinetics of RPC-loaded microspheres

Model	Free RPC		RPC-loaded microspheres
	Equation	Correlation coefficient (r^2)	Equation	Correlation coefficient (r^2)
First order	ln(1− Q) =3.276t −1.092	0.9432	ln(1− Q) =5.276t +0.562	0.9534
Higuchi	Q =8.211t½+1.219	0.9821	Q =8.627t½+1.921	0.9812
Korsmeyer–Peppas	lnQ =0.256lnt −0.627	0.9525	lnQ =1.287lnt +0.192	0.9546
Weibull	lnln(1/(1− Q)) =3.291lnt −1.281	0.9829	lnln(1/(1− Q)) =1.982lnt +0.261	0.9931

Abbreviation: RPC, ropivacaine.

Table 2 Pharmacokinetic parameters of the two formulations

Parameter	Formulations
	Injection	Microspheres
t½ (hours)	1.79±0.65	9.13±3.32
Cmax(ng/mL)	856.5±121.4	569.4±126.3*
AUC0–t(ng⋅h/mL)	5,439.6±541.7	23,210.2±2,315.4*
AUC0–∞(ng⋅h/mL)	5,864.9±598.2	25,265.6±2,448.6*
CL (L/h)	8.26±1.37	2.14±0.71*

Note:

* P<0.05, RPC injection vs microspheres.

Abbreviations: AUC, area under the concentration–time curve; CL, clearance; C_max, maximum observed concentration; RPC, ropivacaine; t_½, elimination half-life.

Figure 4 Mean plasma concentration–time profiles for free RPC (◊, jade) and RPC-loaded chitosan microspheres (Δ, purple) administered to rats.

Note: Each point represents the mean ± standard deviation of six rats.
Abbreviation: RPC, ropivacaine.

Figure 5 Pharmacodynamic evaluation of RPC in different formulations administered to mice.

Note: Each point represents the mean ± SD of 12 mice.
Abbreviations: RPC, ropivacaine; SD, standard deviation.