A new approach for treatment of precancerous lesions with curcumin solid–lipid nanoparticle-loaded gels: in vitro and clinical evaluation

Figures & data

Table 1. Composition of conventional curcumin mucoadhesive gels.

	Ingredients (w/w %)
Formulae code	Polycarbophil	Poloxamer 407	PEG-cocoate	Curcumin	PEG400	Water to
P0.5PX40720	0.5	20	1	1.2	10	100
P1PX40720	1	20	1	1.2	10	100
P2PX40720	2	20	1	1.2	10	100
P1PX40710	1	10	1	1.2	10	100
P2PX40710	2	10	1	1.2	10	100
P3PX40710	3	10	1	1.2	10	100
Curcumin solid–lipid nanoparticle-loaded gel
CurSLN-gel	2	2	–	CurSLN dispersion	–	100

CurSLN dispersion: curcumin solid–lipid nanoparticles containing 0.6% curcumin, 5% gelucire and 8% poloxamer 407.

P, polycarbophil; PX407, poloxamer 407, subscripts denotes concentration (w/w %).

Figure 1. Modified balance for determination of detachment force.

Table 2. Characterization of patients integrated in clinical investigation.

Item	Category	GA (n = 5)^a	GB (n = 5)^b
Gender	Male	3	4
	Female	2	1
Age (in years)		40–54	43–56
Location of erythroplakia	Cheek	4	3
	Tongue	–	–
	Soft palate	1	2
Pain	Yes	5	5
	No	–	–
Pathology	Mild dysplasia	2	1
	Moderate dysplasia	3	2
	Sever dysplasia	–	2

^aGA, patients treated with formula P₂PX407₁₀.

^bGB, patient s treated with formula CurSLN-gel.

Table 3. Physical characterization of formulated curcumin mucoadhesive gels: viscosity, mucoadhesion, spreadability and in vivo residence time.

Formulae codes	Viscosity (cP)	Spreadability (cm)	Mucoadhesion (dyne/cm^2)	In vivo residence time (min)
Conventional curcumin mucoadhesive gels
P0.5PX40720	11 750	2.9	8232.00	20
P1PX40720	15 200	2.7	19 083.27	22
P2PX40720	19 300	2.5	31 805.45	22
P1PX40710	12 800	3.5	13 096.36	5
P2PX40710	13 300	3.3	17 960.72	25
P3PX40710	14 755	3.3	19 956.36	23
Curcumin solid–lipid nanoparticle-loaded gel (CurSLN-gel)
CurSLN-gel	13 800	3.3	1786.29	25

P, polycarbophil, PX407, poloxamer, subscripts denotes concentration in w/w %.

Figure 2. (A) In vitro release profiles (dialysis method) of CurSLN-gel in comparison to conventional curcumin mucoadhesive gel P₂PX407₁₀ and CurSLN dispersion [dissolution medium: 10 ml ethanol:Water (1:1)] at 37 °C. (B) In vitro release profiles (cup method) of CurSLN-gel in comparison to conventional curcumin mucoadhesive gel P₂PX407₁₀ (dissolution medium: 20 ml phosphate buffer, pH 6.8, 0.5% SLS) at 37 °C.

Table 4. Release models of formulated curcumin mucoadhesive gels.

	Zero order	First order	Higuchi	Korsmeyer– Peppas
Formulae code	r^2	r^2	r^2	r^2	n
P2PX40710	0.9893	0.9723	0.8506	0.9842	0.962
CurSLN-gel	0.9969	0.9762	0.8745	0.9963	1.001

Figure 3. Amount of curcumin detected in dissected chicken buccal mucosa after 3 h of permeation test at 37 °C.

Figure 4. Chicken buccal mucosal tissue stained with osmic acid: (A) after CurSLN-gel was applied for 3 hours and (B) control.

Figure 5. Effective pain index %, after 3, 7 and 10 days of follow-up.

Figure 6. % Reduction of lesion size after 2, 4 and 6 weeks of treatment study period.

Figure 7. Severe epithelial dysplasia before the treatment showing acanthotic epithelium with drop shape rete pege’s process (H&E ×200).

Figure 8. (A) Large cell showing abnormal mitotic figures, (B) basilar hyperplasia in basal cell layer, (C) liquification in basal cell layer and basement membrane with multiple mitotic figure and (D) apoptotic cell (civatte body) with clearance of cytoplasm and characteristic chromatin condensation (H&E ×400).

Figure 9. Showing disappearance of epithelial dysplasia after 6 weeks of curcumin treatment.

Figure 10. Patient suffering oral erythoplakia (A) before treatment, (B) after 3 weeks and (C) after 6 weeks (treated with CurSLN-gel).

Figure 11. Patient suffering oral erythoplakia: (A) before treatment, (B) after 3 weeks, (C) after 5 weeks and (D) after 6 weeks (treated with CurSLN-gel).

Figure 12. Patient suffering oral erythoplakia: (A) before treatment, (B) after 3 weeks and (C) after 6 weeks (treated with CurSLN-gel).