Biomaterials for Ocular Drug Delivery

The task of adequately delivering drugs to the eye especially retina is challenging due to limited access to the retina and the presence of blood ocular barriers. We have developed subconjunctivally implantable/injectable hydrogels/nanogels for aqueous loading of insulin with >95% loading efficiency, and sustain release of insulin to the retina to treat diabetic retinopathy.  Our hydrogel/nanogel technology provides single administration to avoid repeated injections which may cause damage to the surrounding tissues to increase patient compliance. The hydrogels/nanogels can degrade into small harmless molecules after a desired period of time and require no surgical removal. Besides continuing to develop the hydrogel/nanogels technology for the treatment of diabetic retinopathy, we are leveraging the technology as a drug delivery platform for controlled release of drugs with desired local doses and durations to treat other ocular diseases such as proliferative vitreoretinopathy, glaucoma, age-related macular degeneration, uveitis, and retinoblastoma, etc.

Imai H, Misra GP, Wu LF, Janagam DR, Gardner TW and Lowe TL. Investigative Ophthalmology & Visual Science 56:7839-7846, 2015.
Lowe TL, Kim YS and Huang X. U.S. Patent No. 8,545,830, 2013.
Misra GP, Singh RS, Aleman TS, Jacobson SG, Gardner TW, and Lowe TL. Biomaterials 30:6541-6547, 2009.
Huang X, Misra GP, Vaish A, Flanagan JM, Sutermaster B and Lowe TL. Macromolecules 41: 8339–8345, 2008.
Huang X and Lowe TL. Biomacromolecules 6: 2131-2139, 2005.

Nanotechnology for Brain Drug Delivery

Many drugs have attracted growing interest for the treatment of a variety of brain diseases. The use of these drugs, however, is still hampered by the lack of an effective route and method of delivery. The reason is because these drugs have very short half-lives, do not cross the blood-brain barrier (BBB) and are easily metabolized at other tissue sites. We have developed β-cyclodextrin-based nanoparticles for sustained delivery of doxorubicin across the BBB. Currently we continue our efforts on developing a variety of novel nanoparticles with tailored architectures and properties of hydrophilicity, hydrophobicity, charge density and hydrolytic degradation for targeted and sustained drug delivery across the BBB to treat Alzheimer’s disease, glioblastoma, and other diseases in the brain.

Gil ES, Wu LF, Xu LC and Lowe TL. Biomacromolecules 13: 3533-41, 2012.
Gil ES, Li JS, Xiao HN and Lowe TL. Biomacromolecules 10:505-516, 2009.

Biomaterials for Responsive Drug Delivery in Cancer Therapy

Our group developed thermoresponsive and biodegradable linear dendritic nanoparticles for thermally targeted and sustained delivery of ceramide to treat breast cancer. We continue to optimize the nanoparticles for more efficient targeted drug delivery in response to temperature as well as biological stimuli to treat cancer and other chronic diseases.

Kester M, Stover T, Lowe TL, Adair JH and Kim YS. U.S. Patent No. 9,028,863, 2015.
Lowe TL, Kim YS and Huang X. U.S. Patent No. 8,916,616, 2014.
Stover TC, Kim YS, Lowe TL and Kester M. Biomaterials 29 (3): 359-369, 2008.
Kim YS, Gil ES and Lowe TL. Macromolecules 39: 7805-7811, 2006.

Biomaterials for Non-enzymatic Cell Harvesting for Cartilage & Bone Repairs

Current clinical approaches for repairing injured cartilage tissues involve transplants that have donor limitation and other difficulties. Tissue engineering concept suggests that obtaining a small quantity of chondrocytes and expanding cell volume in vitro before transplantation may facility regeneration of cartilage tissue. We engineered porous, chemically crosslinked, thermoresponsive and partially biodegradable hydrogels that could be used as 3-D scaffolds to grow chondrocytes and then non-enzymatically harvest the cells at room temperature to maintain the cell phenotype for cartilage repair. In addition, we also developed thermoresponsive block polymers as 2-D supporting film materials for osteoblasts to grow and then a sheet of the cells to be harvested non-enzymatically for bone regeneration. We continue to develop biomaterials that can provide 2-D and 3-D environments to promote cell growth, differentiation and non-enzymatic harvesting with tunable chemical, physical and mechanical cues for cartilage and bone repairs.

Kim YS, Lim JY, Donahue HJ and Lowe TL. Tissue Engineering 11: 30-40, 2005.
Huang X, Zhang Y, Donahue HJ and Lowe TL. Tissue Engineering 13: 2645-2652, 2007.

Long-acting Injectable In Situ Gelling Depot Systems for Improved Family Planning and Global Health

In clinical practice, there is an urgent need for injectable long-acting reversible contraceptives which can provide contraceptive protection for more than 3 months after single injection. Availability of such products will offer great flexibility to women and resolve certain continuation issues currently occurring in clinics, especially in developing countries. To meet this need, we have developed subcutaneously injectable in situ gelling depot systems for sustained release of contraceptives for more than six months after single injection. These injectable systems outperform current commercial products Depo-Provera®/Depo-subQ Provera 104® in term of duration (>6 vs. 3 months), and Eligard® in terms of needle size (21-23 vs. 19-19 G) and initial burst (5-8 vs. 60-300 times). We developed LC/MS/MS method for detecting levonorgestrel in rat plasma and apply the method to study the pharmacokinetics of levonorgestrel in rats after SubQ injection. We continue to optimize the injectable in situ gelling depot systems for robust 6-12 month contraception.

Janagam DR, Ananthula, S, Chaudhry K, Wu LF, Mandrell TD, Johnson JR and Lowe TL. Advanced Biosystems. Available online August 25, 2017.
Ananthula, S, Janagam DR, Jamalapurama S, Johnsona JR, Mandrell TD and Lowe TL. Journal of Chromatography B 1003:47–53, 2015.
Lowe TL, Johnson JR and Wu LF. In-Situ Gelling Form for Long-Acting Drug Delivery. U.S. Patent Pending.