Mengwen Zhang, Maksymilian Nowak, Paula Malo de Molina, Michael Abramovitch, Katherine Santizo, Samir Mitragotri, and Matthew E Helgeson. 2017. “Synthesis of Oil-Laden Poly(ethylene glycol) Diacrylate Hydrogel Nanocapsules from Double Nanoemulsions.” Langmuir, 33, 24, Pp. 6116-6126.Abstract
Multiple emulsions have received great interest due to their ability to be used as templates for the production of multicompartment particles for a variety of applications. However, scaling these complex droplets to nanoscale dimensions has been a challenge due to limitations on their fabrication methods. Here, we report the development of oil-in-water-in-oil (O/W/O) double nanoemulsions via a two-step high-energy method and their use as templates for complex nanogels comprised of inner oil droplets encapsulated within a hydrogel matrix. Using a combination of characterization methods, we determine how the properties of the nanogels are controlled by the size, stability, internal morphology, and chemical composition of the nanoemulsion templates from which they are formed. This allows for identification of compositional and emulsification parameters that can be used to optimize the size and oil encapsulation efficiency of the nanogels. Our templating method produces oil-laden nanogels with high oil encapsulation efficiencies and average diameters of 200-300 nm. In addition, we demonstrate the versatility of the system by varying the types of inner oil, the hydrogel chemistry, the amount of inner oil, and the hydrogel network cross-link density. These nontoxic oil-laden nanogels have potential applications in food, pharmaceutical, and cosmetic formulations.
Amrita Banerjee, Kelly Ibsen, Yasunori Iwao, Michael Zakrewsky, and Samir Mitragotri. 2017. “Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent.” Adv Healthc Mater, 6, 15.Abstract
Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa). CAGE enhances permeation of BSA, OVA, and insulin into porcine skin ex vivo, penetrating deep into the epidermis and dermis. Studies using tritium-labeled BSA and fluorescein isothiocyanate labeled insulin show significantly enhanced delivery of proteins into and across porcine skin, penetrating the skin in a time-dependent manner. Fourier transform IR spectra of porcine stratum corneum (SC) samples before and after incubation in CAGE show a reduction in peak area attributed to SC lipid content, suggesting lipid extraction from the SC. Circular dichroism confirms that CAGE does not affect insulin's secondary conformation. In vivo studies in rats show that topical application of 10 U insulin dispersed in CAGE (25 U kg insulin dose) leads to a highly significant 40% drop in blood glucose levels in 4 h that is relatively sustained for 12 h. Taken together, these studies demonstrate that CAGE is a promising vehicle for transdermal delivery of therapeutic proteins; specifically, as a noninvasive delivery alternative to injectable insulin for the treatment of diabetes.
AC Anselmo and S Mitragotri. 2016. “A Chemical Engineering Perspective of Nanoparticle-based Targeted Drug Delivery: A Unit Process Approach.” AIChE., 62, 4, Pp. 966-974.
M Zakrewsky, A Banerjee, S Apte, T Kern, MR Jones, RE Del Sesto, A Kopposch, DT Fox, and S Mitragotri. 2016. “Choline and geranate deep eutectic solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.” Advanced Healthcare Materials, 5, 11, Pp. 1282-1289.
K Camacho, S Menegatti, D Vogus, A Pusluri, Z Fuchs, M Jarvis, M Zakrewsky, M Evans, and S Mitragotri. 2016. “DAFODIL: A novel liposome-encapsulated synergistic combination of doxorubicin and 5FU for low dose chemotherapy.” Journal of Controlled Release, 229, Pp. 154-162.
S Menegatti, M Zakrewsky, S Kumar, J Oliveira, JA Muraski, and S Mitragotri. 2016. “De novo Design of Skin-penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs.” Advanced Healthcare Materials, 5, 5, Pp. 602-609.
V Gupta, BH Hwang, N Doshi, A Banerjee, AC Anselmo, and S Mitragotri. 2016. “Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices.” Annals of Biomedical Eng., Annals of Biomedical Engineering, 44, 6, Pp. 1993-2007.
D Pan, B. Zern O Vargas-Morales, AC Anselmo, V Gupta, M Zakrewsky, S Mitragotri, and V Muzykantov. 2016. “The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells.” PloS one, 11, 3, Pp. e0152074.
M Zakrewsky, JA Muraski, and S Mitragotri. 2016. “Energy-Dependent Internalization of SPACETM Peptide for Rapid Drug Delivery into the Cytoplasm of Human Epidermal Keratinocytes”.
AC Anselmo and S Mitragotri. 2016. “Impact of Particle Elasticity on Particle-Based Drug Delivery Systems.” Advanced Drug Delivery Reviews.
A Banerjee, JH Lee, and S Mitragotri. 2016. “Intestinal Mucoadhesive Devices for Oral Delivery of Insulin”.
K Camacho, S Menegatti, and S Mitragotri. 2016. “Low-molecular-weight-Polymer-drug Conjugates for Synergistic Anticancer Activity of Camptothecin and Doxorubicin Combinations.” Nanomedicine, 11, 9, Pp. 1139-1151.
M Zakrewsky, JA Muraski, and S Mitragotri. 2016. “Mechanistic Analysis of Cellular Internalization of a Cell-and Skin-Penetrating Peptide.” Regenerative Engineering and Translational Medicine, 2, 1, Pp. 23-26.
J Myserson, AC Anselmo, Y Liu, S Mitragotri, D Eckmann, and V Muzykantov. 2016. “Non-affinity factors modulating vascular targeting of nano- and microcarriers.” Advanced Drug Delivery Reviews, 99, PartA, Pp. 97-112.
C Villa, AC Anselmo, S Mitragotri, and V Muzykantov. 2016. “Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems”.
A Banerjee, J Qi, R Gogoi, J Wong, and S Mitragotri. 2016. “Role of nanoparticle size, shape and surface chemistry in oral drug delivery.” Journal of Controlled Release, 238, Pp. 176-185.
Michael Zakrewsky and Samir Mitragotri. 2016. “Therapeutic RNAi robed with ionic liquid moieties as a simple, scalable prodrug platform for treating skin disease.” J Control Release, 242, Pp. 80-88.Abstract
The high prevalence of skin diseases and their visible symptoms result in major physical, emotional, and economic burden for which few solutions exist. To address this unmet medical need, topical delivery of RNAi such as siRNA holds many advantages including direct access to the diseased site, potent knockdown of disease symptoms, and limited off-target effects. Unfortunately, delivering drugs into skin is extremely difficult. To address these concerns, we present RNAi robed with ionic liquid moieties. Specifically, we show that robed-siRNAs can be synthesized by a simple two-step process from bulk materials. Robing affords tuneability of properties necessary for dermal drug delivery including octanol-water partitioning, skin transport, and cell internalization. The efficacy and safety of robed-siRNA for treating skin disease was confirmed by its ability to limit breakdown of elastin, a major cause of premature aging, following UVB exposure to human reconstructed skin tissue. Together, the data strongly support that therapeutic RNAi robed with ionic liquid moieties are a simple, scalable prodrug platform for treating skin disease.
S Mitragotri, DG Anderson, X Chen, EK Chow, D Ho, AV Kabanov, JM Karp, K Kataoka, CA Mirkin, SH Petrosko, J Shi, MM Stevens, S Sun, S Teoh, SS Venkatraman, Y Xia, S Wang, Z Gu, and C Xu. 2015. “Accelerating the Translation of Nanomaterials in Biomedicine.” ACS Nano, 9, 7, Pp. 6644-6654.
A Anselmo and S Mitragotri. 2015. “Biomimetic Engineering of Particles: Synthetic Cells.” Indian CRS Newsletter.
AC Anselmo, M Zhang, S Kumar, DR Vogus, S Menegatti, and ME Helgeson et al. 2015. “Elasticity of Nanoparticles Influences Their Blood Circulation, Phagocytosis, Endocytosis and Targeting.” ACS Nano, 9, 3, Pp. 3169-3177.