The dissolution and bioavailability of curcumin reinforced by loading into porous starch under solvent evaporation

Curcumin is a polyphenol with anti-inflammatory and antitumorigenic properties. However, its low water solubility and bioavailability limit its use. In this study, porous starch supplemented with a solvent evaporation process was demonstrated as a highly loaded vehicle for curcumin (17.82 %) that could be efficiently solubilized over sustained periods. The migration of curcumin and its adsorption onto the surface of porous starch during solvent evaporation indicated that curcumin was deposited as amorphous globules in pores and encapsulated on the starch surface.

Highlights

• Solvent evaporation is beneficial to the increase of drug loading and dissolution of CU/PS.
• Contributions of hydrophobic interactions and OH-π hydrogen bonding were confirmed.
• CU/PS enhanced cellular uptake and reduced IC50 of raw curcumin by 55 times in Caco-2 cells.

The process was demonstrated to involve hydrogen bonding and hydrophobic interactions using infrared spectroscopy and particle dissociation experiments. Notably, the saturated solubility of curcumin in CU/PS in ionized water, ethanol, and acetic acid was 17.81×, 31.65×, and 26.53× greater than that of raw curcumin, respectively. In particular, it could slowly dissolve in simulated intestinal fluids and exhibited a higher cumulative dissociation (about 6 times that of raw curcumin).

In vitro experiments using a colon adenocarcinoma cell line confirmed that curcumin loaded with porous starch enhanced cellular uptake and reduced IC₅₀ of raw curcumin by 55 times. Thus, porous starch with a simple and efficient process provides new ideas for the design of drug delivery systems and is expected to inspire further development in reducing dosing intervals and maximizing therapeutic efficacy.

Introduction

Curcumin is a naturally occurring polyphenolic compound extracted from turmeric (Curcuma longa) that is of interest to the pharmaceutical and food industries because of its wide range of beneficial bioactivities, such as antioxidant, anti-inflammatory, and anticancer activities [[1], [2], [3]]. However, poor solubility/bioavailability and also instability of curcumin have limited its application as health-promoting agent [[4], [5], [6]]. Limited solubility hinders drug bioavailability and lead to significant side effects. These side effects are due to dose escalation, which is necessary in the case of poorly soluble drugs, and are particularly evident in gastrointestinal irritation [7]. Therefore, it is necessary to develop delivery systems that provide sustained curcumin release and focus on reducing drug particle size and crystal form changes.

One of the most common approaches is to prepare curcumin mixtures with various additives and excipients, such as solid dispersions (molten mixtures, co-crystallized forms, co-amorphous mixtures, soluble polymer composites) with improved solubility and bioavailability [8]. Besides, different delivery systems have been reported for curcumin, including lipid-based [9], chemical polymer- and biopolymer-based, nature-inspired [10,11], special equipment-based [12] and surfactant-based [13] techniques. However, the methods used to produce these systems are characterized by low drug loading (<15 %) and delivery efficiency, cumbersome processes, or chemical residues.

The need for biocompatible materials to facilitate metabolite transport was emphasized by Wichterle and Lim in 1960 [14], who highlighted possible structural and biological incompatibilities between conventional plastics and living tissues. Since then, natural polymeric materials have attracted significant interest in biomedical research [[15], [16], [17], [18]]. Porous starch is an enzymatic product of native starch and is a biodegradable, slow-release carrier. The unique curved channels of porous starch prolong storage stability by preventing the exposure of guest molecules to light, oxygen, and moisture. Most of the components in starch pores are amorphous, significantly increasing their solubility and bioavailability (e.g., paclitaxel [19], lovastatin [20], melatonin [21] and carbamazepine [22]). In the case of hydrophobic probucol, porous starch increased its distribution in the duodenum, jejunum, and ileum by 7.17×, 15.99×, and 33.61×, respectively [23]. However, most conventional impregnation methods tend to have longer equilibration times and poor adsorption properties, making it difficult to realize the payload of porous starch. As such, we hypothesize that the dissolution of curcumin can be significantly improved after adsorption by porous starch, thereby improving its bioavailability.

In this study, curcumin was loaded onto porous starch via a rapid and simple solvent volatilization process. By monitoring the adsorption process, we elucidated the distribution of curcumin on porous starch and its crystalline state, and thereafter explored the intermolecular interactions. We compared the solubility of the resulting curcumin preparation in different solutions with that of the raw drug and determined their dissolution profiles in simulated intestinal fluid. In addition, by observing cellular uptake and apoptosis, porous starch-loaded curcumin was shown to be more accessible and toxic to cancer cells.

Read more here

Get to know the interesting  TaBlitz Software:

TaBlitz™ – Redefining the tablet design process

DIRECT CONTACT TO TABLITZ