Solid Lipid Nanoparticles Improve the Diclofenac Availability in Vitreous after Intraocular Injection.

Purpose. In order to improve the drug availability after intravitreal administration, solid lipid nanoparticles (SLNs) containing diclofenac were prepared. Methods. In this experimental study, 18 albino rabbits were included. In right and left eyes of all rabbits, SLNs containing diclofenac and commercial form of diclofenac (0.3 mg drug) were intravitreally injected, respectively. One, four, twelve, twenty-four, and forty-eight hours after injection, vitreous and aqueous humor samples were obtained in all cases. Then, the concentration of diclofenac sodium was evaluated in all samples. Results. Size of nanoparticles was around 170 nm after preparation. Drug concentration in eyes injected with SLNs was significantly higher than left eyes injected with commercial formulation up to 4 hours after intravitreal injection (p < 0.05). Diclofenac was quantified in samples up to 48 hours after intraocular injection. Four hours after intravitreal injection, the concentration of diclofenac in vitreous and aqueous humor of eyes receiving SLNs was, respectively, 2.5 and 6.5 times higher than eyes injected with commercial form of drug. Conclusions. Here, we demonstrate the potential of SLNs as a carrier of diclofenac for intraocular injection in order to prevent the systemic effects of the drug, increase the injection intervals, and improve the patient compliance.

Solid lipid nanoparticles containing 7-ethyl-10-hydroxycamptothecin (SN38): Preparation, characterization, in vitro, and in vivo evaluations.

7-Ethyl-10-hydroxycamptothecin (SN38) is a biologically active metabolite of irinotecan. Due to the variability of irinotecan metabolism rate to SN38, and poor solubility of this compound in pharmaceutically acceptable solvents, SN38 has not been successfully used in the clinic. In the present study, we prepared solid lipid nanoparticle (SLN) formulations containing SN38 and evaluated the in vitro and in vivo efficacy of these nanoparticles. SLNs and PEGylated SLNs containing SN38 (SLN-SN38 and PEG-SLN-SN38) were prepared using ultrasonication technique. Nanoparticles were characterized for size, zeta potential, and drug encapsulation efficiency. In vitro cytotoxicity of these compounds was evaluated in two colorectal carcinoma cell lines, namely C-26 and HT-116. In vivo antitumor efficacy of the formulations was evaluated in C-26 xenograft tumor mice models. Mice survival was also explored through 60days post IV injection. Mean size of SLN-SN38 and PEG-SLN-SN38 was around 103 and 131nm, respectively. Polydispersity index (PDI) for all the formulations was around 0.2 and zeta potential was negative (-5 to -15mV). Nearly 90% of the drug was encapsulated in SLNs. SLN-SN38 and PEG-SLN-SN38 compared to irinotecan were significantly more toxic to C-26 and HT-116 cell lines after 48h of exposure. Calculation of IC50 suggests higher sensitivity of HT-116 cells than C-26 cells to SLN-SN38 and PEG-SLN-SN38. Tumor inhibitory efficacy presented the highest efficacy in SLN-SN38. However, both SLN-SN38 and PEG-SLN-SN38 carriers showed higher efficiency to inhibit tumors compared to irinotecan (25mg/kg).

Preparation, characterization, and moisturizing effect of liposomes containing glucosamine and N-acetyl glucosamine.

BACKGROUND: N-acetyl glucosamine (NAG) is a precursor for hyaluronic acid (HA) biosynthesis in the body. The main role of HA is to preserve the hydration and elasticity of the skin. AIMS: To prepare and characterize liposomes containing N-acetyl glucosamine and glucosamine (GA) and to assess their effects on the skin moisture content. METHODS: Liposomal formulations containing NAG and GA were prepared using fusion and dehydration-rehydration (DRV) methods. The amount of the moisture contents of the skin before application and 0.5, 1, 3, and 5 h postapplication of the formulations were measured in human volunteers using corneometer. The occlusive factor was also estimated by in vitro method. RESULTS: Mean size of prepared liposomes was <2 µm, and all formulations showed negative surface charge. The highest effect on skin moisture content was achieved by NAG liposomal prepared using fusion method after 3 h. The difference between moisture content of the skin treated by preparations containing GA (solution and liposomes) and empty liposomes was negligible in all tests and duration times of the experiment. The results of the moisturizing effect according to the in vivo method indicated that there was a significant difference (P < 0.05) between the skin moisture contents after application of liposomal formulation containing NAG 7 mm and empty liposomes during the 5-h postapplication period. CONCLUSIONS: Our study demonstrated the potential of liposomes for improved NAG localization in the skin, and so it could be suggested as a new topical moisturizing formulation in skin care products.

Docetaxel-loaded solid lipid nanoparticles: preparation, characterization, in vitro, and in vivo evaluations.

The aim of the present study was to prepare, characterize, and evaluate solid lipid nanoparticles (SLNs) containing docetaxel (DTX) to improve the efficacy of this chemotherapeutic agent. SLNs containing DTX (SLN-DTX) were prepared by microemulsion and probe sonication techniques. In vitro cytotoxicity of SLN-DTX compared with Taxotere® (TXT) was evaluated on colorectal (C-26) and malignant melanoma (A-375) cell lines. Cellular uptake experiment was also carried out on C-26 cells. In in vivo tests, tumor inhibitory efficacy and survival were compared with TXT on C-26-implanted BALB/c mice. SLN-DTX particle size was 180 nm and PDI of 0.2 with spherical shape. Encapsulation efficacy was more than 98%. SLN-DTX at concentration of 100 µM caused 100% and 99.9% viability reduction in C-26 and A-375 after 48 and 72 h, respectively. The half maximal inhibitory concentration (IC50 ) of SLN-DTX on C-26 and A-375 was respectively 0.769 and 28.132 µM after 24 h. DTX cell uptake from SLN-DTX was remarkably higher than TXT. SLN-DTX showed better tumor inhibitory efficacy and survival at a dose of 10 mg/kg versus 10 and 20 mg/kg TXT. In conclusion, the results of the present study showed that the efficacy of SLN-DTX was better than TXT in cell-uptake and in vivo experiments.

Safety evaluation of nanoliposomes containing cyclosporine a after ocular administration.

AIM: Cyclosporine A (CyA) is an anti inflammatory drug which modulates immune system. We prepared two liposomal formulations of CyA for ophthalmic administration. In the present study, the safety of these formulations was tested in rabbits. MATERIALS AND METHODS: Fusogenic and positively charged liposomes were prepared by solvent evaporation method. CyA concentration in ophthalmic preparations was 0.2% w/v. Twenty New Zealand albino rabbits (40 eyes) were divided into two groups. Right eyes were treated and left eyes served as control. Eyes were examined clinically in 1, 3, 7, 14 and 28th days of the study. Eleven eyes were enucleated for pathological evaluation at the end of the study. RESULTS: Mean size and charge of positively charged and fusogenic liposomes were 110.7 ± 1.5 and 114.9 ± 15.2 nm; 19.0 ± 2.2 and 2.5 ± 0.5 mV, respectively. Clinically, there were transient conjunctival injections and corneal epithelial defects in a few cases which were not limited to the treated eyes. Positively charged liposomes caused conjunctival injection in two cases, while this complication occurred in only one eye after administration of fusogenic liposomes. Histopathological examination revealed the presence of follicular conjunctivitis in two eyes with conjunctival injection. Inflammation in cases received the fusogenic form of the drug was mild and non-specific. CONCLUSIONS: The results of this study suggest that fusogenic liposomal preparation of CyA is safe and can be useful for future studies.