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Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation

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Abstract

The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D’s oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention.

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Acknowledgments

The authors would want to express their gratitude to Dr. Jagan M. Somagoni for his contribution to this study.

This project was supported by the NIH Minority Biomedical Research Support (MBRS)-SC1 program [Grant # SC1 GM092779-01; MS] and the National Institute of Minority Health and Health Disparities (NIMHD) NIMHD P20 [Grant # 1P20 MD006738-03; MS].

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Authors and Affiliations

  1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1520 S Martin Luther King Jr. Blvd, Tallahassee, FL, 32307, USA

    Cedar H. A. Boakye, Ketan Patel, Apurva R. Patel & Mandip Singh

  2. Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, USP, São Carlos, SP, 13566-590, Brazil

    Henrique A. M. Faria & Valtencir Zucolotto

  3. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA

    Stephen Safe

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  1. Cedar H. A. Boakye
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Correspondence to Mandip Singh.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Boakye, C.H.A., Patel, K., Patel, A.R. et al. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation. Drug Deliv. and Transl. Res. 6, 526–539 (2016). https://doi.org/10.1007/s13346-016-0302-2

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