ABSTRACT
The solid self-nanoemulsifying drug delivery system (s-SNEDDS) is a growing platform for the delivery of drugs via oral route. In the present work, tamoxifen (TAM) was loaded in SNEDDS with resveratrol (RES), which is a potent chemotherapeutic, antioxidant, anti-inflammatory and P-gp inhibitor for enhancing bioavailability and to obtain synergistic anti-cancer effect against breast cancer. SNEDDS were developed using capmul MCM as oil, Tween 80 as surfactant and transcutol-HP as co-surfactant and optimized by central composite rotatable design. Neusilin US2 concentration was optimized for adsorption of liquid SNEDDS to prepare s-SNEDDS. The developed formulation was characterized and investigated for various in vitro and cell line comparative studies. Optimized TAM-RES-s-SNEDDS showed spherical droplets of a size less than 200 nm. In all in vitro studies, TAM-RES-s-SNEDDS showed significantly improved (p Ë 0.05) release and permeation across the dialysis membrane and intestinal lumen. Moreover, TAM-RES-s-SNEDDS possessed significantly greater therapeutic efficacy (p < 0.05) and better internalization on the MCF-7 cell line as compared to the conventional formulation. Additionally, oral bioavailability of TAM from SNEDDS was 1.63 folds significantly higher (p < 0.05) than that of combination suspension and 4.16 folds significantly higher (p < 0.05) than TAM suspension. Thus, findings suggest that TAM- RES-s-SNEDDS can be the future delivery system that potentially delivers both drugs to cancer cells for better treatment.
ABSTRACT
BACKGROUND: The combination of timolol maleate (TM) and brinzolamide (BRZ) has potential therapeutic prospects for treating glaucoma. However, the conventional formulation of TM and BRZ exhibits sub optimal therapeutic effects attributable to the poor ocular bioavailability of these drugs. OBJECTIVE: Therefore, the aim of the present study was to design and evaluate TM and BRZ loaded nanostructured lipid carrier (NLC) to enhance the bioavailabilities, permeation and precorneal residence time of these drugs that would result in efficacious treatment of glaucoma. METHODS: In this study, combination of drugs with different characteristic properties was loaded in NLC. The dual drugs loaded NLC was prepared by melt emulsification technique and evaluated for characteristic properties such as particle size (PS), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL), in vitro drug release and ex vivo drug penetration studies. RESULTS: The PS and PDI of optimized NLC formulation were found to be 110.36 ±0.47 nm and 0.24 ± 0.00 respectively. The EE and DL of optimized NLC formulation were found to be 77.12 ± 0.64 % and 0.360 ± 0.01 % for TM respectively; whereas, 70.73±0.64 % and 0.71 ± 0.02 %for BRZ respectively. In vitro drug release studies showed a comparable initial rapid release of around 34 ± 2.90 % for TM and 38 ± 3.10 % for BRZ in the first 5 h followed by sustained drug release around 72.29 ± 5.90 % for TM and 70.08 ± 6.40 % for BRZ until last 24 h. Ex vivo drug penetration studies showed about 33.47 ± 2.80 % of TM and 36.20 ± 2.80 % of BRZ permeated in the first 5 h followed by 72.30 ± 6.40% of TM and 67.69 ± 6.500 % of BRZ until 24 h. There was remarkable enhancement in the release pattern and permeation of both the drugs from NLC as compared to that from their suspension. CONCLUSION: With dextrous optimization of dose and excipients concentration, the dual drugs with different characteristic properties can be successfully loaded in NLC formulation.
