Preparation And Evaluation Of Curcumin-loaded Hydrogel

Curcumin(CUR)is a polyphenolic compound extracted from the rhizome of Curcuma longa,a perennial herb.It is widely used in food industry and medical research because of its wide pharmacological activity,low toxicity and side effects,and high safety dose.However,its application in biomedicine is greatly limited due to its poor solubility in water,unstable chemical properties,low oral absorption and rapid intestinal metabolism.Micelle is a class of colloidal solution with hydrophobic core and hydrophilic shell.The hydrophobic segments of micelles self-associate and aggregate in water to form a hydrophobic inner cavity,which can be used as a reservoir of hydrophobic drugs,and hydrophilic segments as hydrophilic outer layers of micelles extend into water to stabilize micelles.Micelle provides a potential drug delivery vehicle for the delivery of hydrophobic drugs.Hydrogel is a three-dimensional cross-linking network structure of water-soluble polymer materials.Hydrogel is characterized by its ability to absorb large amounts of water or biological liquids.Recent studies have found that alpha-cyclodextrin(?-CD)can form cross-linked structures with some polymers with epoxy as repetitive units to prepare hydrogels.The formation of the hydrogel usually consists of two stages:First,the intermolecular forces in the cavity of?-CD can form a linear structure with the guest polymer,and then the interlocking structure can be formed by the hydrogen bond between adjacent?-CD,and the hydrogen bond between?-CD can stabilize the crosslinked network structure.Recently reported guest materials include poly(ethylene glycol)(PEG),Polyethylene oxide(PEO)and monomethoxypolyethylene glycol(MPEG).When the derivatives of the guest materials are used to encapsulate drugs by chemical or physical encapsulation,the corresponding drug loaded micelles can be obtained and mixed with?-CD to obtain hydrogel.In the study,with monomethoxy poly(ethylene glycol)(MW=2KDa)as hydrophilic framework and poly(?-caprolactone)as hydrophobic segment,amphiphilic monomethoxy polyethylene glycol-polycaprolactone(MPEG-PCL)was prepared via ring-opening polymerization,and its structure was confirmed by ~1H-NMR and FT-IR analysis.CUR-loaded micelles(CUR-M)were prepared by film hydration method using MPEG-PCL as material.The preparation process and physicochemical properties of CUR-M were investigated.The results showed that the optimum formulation of CUR-M was as follows:the volume of acetone was 2mL,mass ratio of MPEG-PCL to CUR was 7:1,hydration volume was 5 mL,hydration temperature was 60?C.The encapsulation efficiency and loading quantity of CUR-M obtained by the optimum preparation process were 93.57±1.67%and 12.14±0.33%,respectively.The solubility of CUR in water increased by 1.87×10~6 times,and CUR-M significantly improved the water solubility of drug;the mean particle size and Zeta potential of CUR-M were 48.75±1.90 nm and-13.2±0.8mV,respectively;XRD and FT-IR characterization of CUR-M confirmed that CUR was encapsulated in MPEG-PCL and existed in the amorphous state.CUR-loaded hydrogels(CUR-H)was prepared by physical mixing method with CUR-M and?-CD.The concentration of?-CD and the physicochemical properties of CUR-H in the formulation were investigated,and the dissolution and the experiment of skin penetration and deposition of of CUR-H in the skin were carried out.The results showed that the optimum formulation of CUR-H was as follows:the concentration of?-CD was 180 mg/mL,the volume ratio of CUR-M to?-CD was 2:1(v/v);the average particle size and Zeta potential of CUR-H solution were 50.49±0.94 nm and-14.23±0.12mV,respectively;the stability of CUR-H solution indirectly proved that CUR-H had good stability;XRD and FT-IR characterization confirmed the successful preparation of CUR-H.The results of dissolution experiments showed that CUR-H could be rapidly and continuously corroded in a time-dependent manner,and about 90%of the gel was dissolved in 4.5 h.The skin penetration of CUR-H and the amount of drug deposition in the skin showed that the drug accumulation in the skin of the CUR-H group was 6.23 times higher than that of the physical mixed gel control group,indicating its enhanced skin permeability,and fluorescence microscopy analysis also confirmed this result.In the croton oil-induced acute inflammation model of mouse ear,the anti-inflammatory activity of CUR-H was evaluated with dexamethasone cream as positive control and blank hydrogel as negative control group.After6 h of administration,the results of mouse ear thickness and weight changes showed that CUR-H showed better inflammation inhibitory effect than the commercially available dexamethasone cream,and the histopathological study also confirmed it.In summary,we developed a topical application of CUR-H for the treatment of acute inflammation.The results of dissolution experiment,skin permeability experiment and anti-inflammatory activity study confirmed that CUR-H was suitable for skin administration.This research provides a research basis for the development of safe,highly effective,skin-penetrating gel formulations.