Natural-resin in-situ-forming gels: Physicochemical characteristics and bioactivities

Abstract

An injectable in situ-forming gel (ISG) is a promising approach as a drug delivery system. In this study, natural resins including aloe, benzoin and propolis dissolved in N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO) were investigated as ISG systems for their ability to form matrices in phosphate buffer. Regarding their functions as ISG, their pH values, viscosities, flow behaviours, surface tensions and injectabilities were tested. Benzoin and propolis exhibited greater matrix formation than aloe, owing to their higher resin contents. Benzoin and propolis in DMSO formed matrices with a faster solvent exchange rate compared with those in NMP. The former had a higher viscosity than the latter, but both of them exhibited similar densities and surface tensions. The 35% and 40% w/w benzoin in DMSO exhibited dominant matrix formations with acceptable injectability via syringe. The 35% w/w benzoin and propolis ISG in DMSO efficiently inhibited the growth of Staphylococcus aureus strains, and the propolis ISG also exhibited a clear inhibition zone against Porphyromonas gingivalis, whereas aloe did not. From the cell viability assay, propolis exhibited a higher toxicity against HCT116 colon cancer cells (IC50=95 µg/ml) compared with benzoin (IC50=400 µg/ml), whereas the resin from aloe showed no toxic effect on this cell. Due to their rapid insoluble matrix formation after contacting aqueous fluid as well as their antibacterial and cytotoxic activities against colon cancer cell, the 35% w/w benzoin and propolis in DMSO have the potential for use as a matrix former for ISGs.

Clotrimazole-Loaded Borneol-Based In Situ Forming Gel as Oral Sprays for Oropharyngeal Candidiasis Therapy

“…Therefore, the borneol matrix occurred after phase transformation via solvent removal and retarded the diffusion of antimicrobial agents and NMP from borneol-based ISGs. These results resembled other ISGs fabricated using rosin [40,41], ethyl cellulose [29], and some fatty acids [44][45][46] as matrix-forming materials. An increased concentration of these matrix-forming materials diminished the inhibition zone against pathogens of periodontitis due to their ability to retard drug diffusion into inoculated agar media.…”

“…The abrupt matrix formation of 50BZCN was evident, whereas a step-by-step change from solution to gel state and cloudier matrix was obtained for 40BZCN. This incidence was also observed for other ISGs comprising different concentrations of polymers [29,[35][36][37], natural resins [40][41][42]48], and fatty acids [44][45][46]. In addition, the appropriate concentration of matrix-forming agents from these previous reports reached nearly 40% w/w because of their fast, dense matrix formation that was, however, not too rapid before formulation spreading at the target site.…”

“…Notably, the viscosities of the clotrimazole-loaded borneol-based ISGs were outstandingly lower than previously mentioned on polymer-based in situ forming systems [35][36][37]. In addition, these developed ISGs also showed lower viscosities than natural resin-based ISGs [40][41][42]. These natural resins, including rosin, benzoin, propolis, and aloe, dissolved in DMSO and NMP were employed as the gelling agents of ISGs in which the viscosities of benzoin in NMP and DMSO were 6.61-171.46 and 19.77-137.03 cPs, respectively, compared with propolis in NMP and DMSO (i.e., 119-155 and 80.96-577.90 cPs, respectively) [41].…”

“…In addition, these developed ISGs also showed lower viscosities than natural resin-based ISGs [40][41][42]. These natural resins, including rosin, benzoin, propolis, and aloe, dissolved in DMSO and NMP were employed as the gelling agents of ISGs in which the viscosities of benzoin in NMP and DMSO were 6.61-171.46 and 19.77-137.03 cPs, respectively, compared with propolis in NMP and DMSO (i.e., 119-155 and 80.96-577.90 cPs, respectively) [41]. The rather low viscosities (<20 cPs) of ibuprofen-based ISGs were recently reported using NMP and DMSO as the solvents [43].…”

Levofloxacin HCl-Loaded Eudragit L-Based Solvent Exchange-Induced In Situ Forming Gel Using Monopropylene Glycol as a Solvent for Periodontitis Treatment

“…Doxycycline hyclate-incorporated ISGs for periodontitis treatment using ethyl cellulose and bleached shellac as the polymers have been reported recently [20]. Borneol, lauric acid, and some natural resins (such as propolis, benzoin, and rosin) are currently being applied as matrix-forming agents of ISG for modulating vancomycin HCL and doxycycline hyclate release for periodontitis treatment [21][22][23]. Eudragit RS has been employed as a polymer for the controlled release of doxycycline hyclate from ISG, in which the addition of peppermint oil and polyethylene glycol could modify drug release [24][25][26][27][28].…”