Nigella sativa extract (NSE) was incorporated in alginate microcapsules using aerosolisation and homogenisation methods, respectively, with the aim of delivering high concentrations of the active species, thymoquinone (TQ), directly to sites of inflammation in the colon following oral administration. Encapsulation of NSE was accomplished either by direct loading or diffusion into blank microparticles. Microcapsules in the size range 40-60 µm exhibited significantly higher NSE loading up to 42% w/w and encapsulation efficiency (EE) up to 63% when the extract was entrapped by direct encapsulation compared with 4.1 w/w loading, 6.2% EE when NSE was incorporated by diffusion loading. Sequential exposure of samples to simulated intestinal fluids (SIFs) revealed that the microcapsules suppressed NSE release in simulated gastric fluid (SGF) for 2 h and SIF for 4 h and liberated most of the NSE content (80%) in simulated colonic fluid (SCF) over 18 h. NSE released in SCF at 12 h exhibited antioxidant activity, when measured using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay at levels comparable with the activity of unencapsulated extract. These findings demonstrate the potential of oral alginate microcapsules as highly efficient, targeted carriers for colonic delivery of NSE in the treatment of inflammatory bowel disease.
Polycaprolactone (PCL) matrices loaded with doxycycline were produced by rapidly cooling suspensions of the drug powder in PCL solution in acetone. Drug loadings of 5%, 10%, and 15% (w/w) of the PCL content were achieved. Exposure of doxycycline powder to matrix processing conditions in the absence of PCL revealed an endothermic peak at 65°C with the main peak at 167°C, suggesting solvatomorph formation. Rapid "burst release" of 24%-32% was measured within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C, because of the presence of drug at or close to the matrix surface, which is further confirmed by scanning electron microscopy. Gradual release of 66%-76% of the drug content occurred over the following 14 days. SVF containing doxycycline released from drug-loaded PCL matrices retained 81%-90% antimicrobial activity compared with the nonformulated drug. The concentrations of doxycycline predicted to be released into vaginal fluid from a PCL matrix in the form of an intravaginal ring would be sufficient to kill Neisseria gonorrhoea and many other pathogens. These results indicate that PCL may be a suitable polymer for controlled intravaginal delivery of doxycycline for the treatment of sexually transmitted infections.
Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 μg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 μg/mL. An in vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 μg/mL phenytoin concentration resulted in 75%-82% "scratch closure" after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.
Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to -80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid 'burst release' of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the 'non-formulated' drug in solution form. Basic modelling predicted that the concentration of tinidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration against Trichomonas vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of antiprotozoal agents in the treatment and prevention of sexually transmitted infections.