HOUSTON, TX, United States

Ensysce Biosciences, Inc.

www.ensysce.com
HOUSTON, TX, United States

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Lynn Kirkpatrick D.,Ensysce Biosciences, Inc. | Schmidt W.K.,Ensysce Biosciences, Inc. | Morales R.,Signature Therapeutics, Inc. | Cremin J.,Signature Therapeutics, Inc. | And 3 more authors.
Journal of Opioid Management | Year: 2017

Objective: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential. Methods: In vitro and in vivo methods were used to determine release of OC from PF614 and to show potential μ-opioid receptor activity. Plasma and cerebral spinal fluid levels of OC were evaluated following in vivo IV administration of PF614 in rats. In vitro extraction of OC from PF614 was explored using enzymes, common solvents, and household chemicals at room temperature and elevated temperature over time to determine release of OC from the prodrug. Results: PF614 was stable with in vitro exposure to human plasma, saliva, and liver microsomes or culinary enzyme preparations. PF614 was stable (≥90 percent remaining as intact prodrug) under all room temperature conditions evaluated for 24 hours. At 80 °C for 1 hour, no OC was released. Incubation at 80 °C for 24 hours in vinegar or vodka produced a conversion to OC of 6 percent. Incubation with trypsin at 37 °C converted PF614 approximately stoichiometric to OC with half-life of 4 hours. PF614's penetration of the central nervous system was 83-fold lower than OC and it had a 6.5-fold reduced potency as a μ-opioid agonist. Finally, oral PF614 delivers OC into plasma with an extended-release profile in dogs (reduced Cmax; delayed Tmax). Conclusions: The Bio-Activated Molecular Delivery prodrug design limits the use of PF614 to the intended oral route of delivery with reduced potential for IV or nasal abuse, as it cannot be activated intravenously or nasally to provide an active opioid. Unlike existing opioid formulations, the extended-release profile of PF614 cannot be accelerated by chewing or ex vivo extraction to pharmacologically active substances. © 2017 Journal of Opioid Management,.


Naumov A.V.,Rice University | Naumov A.V.,Ensysce Biosciences, Inc. | Tsyboulski D.A.,Rice University | Tsyboulski D.A.,Tomowave Laboratories, Inc. | And 2 more authors.
Chemical Physics | Year: 2013

Contradictory findings have been reported on the length dependence of optical absorption cross sections and fluorescence quantum yields in single-walled carbon nanotubes (SWCNTs). To clarify these points, studies have been made on bulk SWCNT dispersions subjected to length fractionation by electrophoretic separation or by ultrasonication-induced scission. Fractions ranged from ca. 120 to 760 nm in mean length. Samples prepared by shear-assisted dispersion were subsequently shortened by ultrasonic processing. After accounting for processing-induced changes in the surfactant absorption background, SWCNT absorption was found constant within ±11% as average nanotube length changed by a factor of 3.8. This indicates that the absorption cross-section per carbon atom is not length dependent. By contrast, in length fractions prepared by both methods, the bulk fluorescence efficiency or average quantum yield increased with SWCNT average length and approached an apparent asymptotic limit near 1 μm. This result is interpreted as reflecting the combined contributions of exciton quenching by sidewall defects and by the ends of shorter nanotubes. © 2013 Elsevier B.V. All rights reserved.


Lynn Kirkpatrick D.,Ensysce Biosciences, Inc. | Weiss M.,Ensysce Biosciences, Inc. | Naumov A.,Ensysce Biosciences, Inc. | Bartholomeusz G.,University of Texas M. D. Anderson Cancer Center | And 2 more authors.
Materials | Year: 2012

Carbon nanotubes have many unique physical and chemical properties that are being widely explored for potential applications in biomedicine especially as transporters of drugs, proteins, DNA and RNA into cells. Specifically, single-walled carbon nanotubes (SWCNT) have been shown to deliver siRNA to tumors in vivo. The low toxicity, the excellent membrane penetration ability, the protection afforded against blood breakdown of the siRNA payload and the good biological activity seen in vivo suggests that SWCNT may become universal transfection vehicles for siRNA and other RNAs for therapeutic applications. This paper will introduce a short review of a number of therapeutic applications for carbon nanotubes and provide recent data suggesting SWCNT are an excellent option for the delivery of siRNA clinically. © 2012 by the authors.


Streit J.K.,Rice University | Bachilo S.M.,Rice University | Naumov A.V.,Rice University | Naumov A.V.,Ensysce Biosciences, Inc. | And 3 more authors.
ACS Nano | Year: 2012

A new method is demonstrated for measuring the length distributions of dispersed single-walled carbon nanotube (SWCNT) samples by analyzing diffusional motions of many individual nanotubes in parallel. In this method, termed "length analysis by nanotube diffusion" (LAND), video sequences of near-IR fluorescence microscope images showing many semiconducting SWCNTs are recorded and processed by custom image analysis software. This processing locates the individual nanotubes, tracks their translational trajectories, computes the corresponding diffusion coefficients, and converts those values to nanotube lengths. The deduced length values are then compiled into a histogram of lengths present in the sample. By using specific excitation wavelengths and emission filters, this analysis is performed on selected (n,m) structural species. The new LAND method has been found to give distributions in very good agreement with those obtained by conventional AFM analysis of the same samples. Because it is fluorescence-based, LAND monitors only semiconducting, relatively pristine SWCNTs. However, it is less sensitive to artifacts from impurities and bundled nanotubes than AFM or light scattering methods. In addition, samples can be analyzed with less time and operator attention than by AFM. LAND is a promising alternative method for characterizing length distributions of SWCNTs in liquid suspension. © 2012 American Chemical Society.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 298.07K | Year: 2012

DESCRIPTION (provided by applicant): Ensysce Biosciences Inc. is a biotechnology company located in Houston, TX, exploiting the pionering nanotechnology studies of the late 1996 Nobel Laureate, Dr. Richard Smalley of Rice University. The rights to Dr. Smalley's work on carbon nanotube technology in the area of therapeutics, as well as other critical carbon nanotube patents, have been in-licensed or applied for by Ensysce and the company has initiated a number of research programs to utilize carbon nanotubesto treat cancer including that described herein to deliver short interfering RNAs (siRNA). Ensysce's interest in the single-walled carbon nanotubes (SWCNT) delivery system spans a number of therapeutic modalities including the delivery of RNAis. siRNA, are a type of small segments of double- stranded RNA that are being explored to control cancer growth in a highly specific fashion. However, efficient means are needed to deliver the RNAi into tumor cells. Ensysce's data show that the solubilized SWCNT/siRNAcomplexes delivered to mice intravenously cause little to no toxicity, accumulate in tumor and produce tumor target-protein knockdown and antitumor activity. Ensysce is now exploring means to optimize the tumor accumulation and produce robust antitumor activity. Ensysce data has also shown that circulating the half-life of SWCNT/siRNA complex affect its biodistribution, although complexes with even short t1/2 were found to produce god antitumor activity in human tumor xengrafts in animal models. This proposal will undertake a comprehensive examination of a number of formulations of SWCNT/siRNA to determine their tumor and tissue distribution following intravenous administration. The preparation with the most promising tumor versus tissue distribution will be further examined for antitumor eficacy using siRNA for KRAS. Mutant KRAS (mut-KRAS) is the prototypical undruggable cancer target. It is found in 25% of patient tumors across many cancer types and an estimated 320,000 individuals who will be diagnosed with mut-KRAS in the US in 2012 most of who will die of their disease. There is no treatment for KRAS and finding effective therapies for KRAS is arguably the single most important unmet medical need in cancer today. Therefore reducing its presence with siRNA delivered by SWCNT provides approach to this deadly problem. Hence, this project will extensively evaluate the biodistribution properties of a number of SWCNT complexes delivered systemically and will provide data on the efficacy of SWCNT/siRNA complexesin tumors. Ultimately, this work will pave the way for the use of a powerful new siRNA delivery system with the potential for inhibiting many different cancer causing targets in a clinical setting for the treatment of cancer. PUBLIC HEALTH RELEVANCE: Novel selective cancer therapies are still needed to improve outcome for patients without unnecessary toxic side effects. Short interfering RNA (siRNA) is one such potential modality as it can block the activity of genes that are essential for the cancer growth but not for normal tissue. However, the major barrier to the development of clinical siRNA therapies is the lack of an effective delivery mechanism to administer it to a patient and carry it into the tumor cell. Ensysce's research has shown that single-walled carbon nanotubes (SWCNT) can complex with siRNA and act as a delivery vehicle to carry siRNA into cancer cells hence providing a selective therapeutic outcome. To ensure delivery of the siRNA to tumors it has been found that the circulationtime (half-life) of the complexes is important. This proposal will undertake a comprehensive examination of a number of SWCNT preparations with a range of circulation half-lives to determine the tumor and tissue distribution following intravenous administration. The preparation with the most promising tumor versus tissue distribution will be further examined for antitumor activity in combination with another cancer therapy. These critical studies will move this novel technology one step closer to full pre-clinical development and eventually to a clinical trial study.


The present invention provides single-walled carbon nanotube formulations for the delivery of bioactive agents including large polynucleotides encoding therapeutic proteins into hard-to-transfect cells and methods of making such single-walled carbon nanotube formulations.


Patent
Ensysce Biosciences, Inc. | Date: 2011-07-01

The present invention includes single-walled carbon nanotube compositions for the delivery of bioactive agents and methods of making such single-walled carbon nanotube compositions.


Ensysce Biosciences, Inc. | Entity website

Scientific Advisory BoardRobert Kaiko, PhDDr. Robert F ...


HOUSTON--(BUSINESS WIRE)--Ensysce Biosciences Inc. efforts in the development of the single walled carbon nanotube (SWCNT) delivery platform for therapeutic applications has led to the important finding that SWCNT can transfect peripheral blood mononuclear cells (PBMCs) following intravenous administration. Ensysce has data demonstrating that SWCNT form stable complexes with oligonucleotide payloads, including full length RNA and plasmid DNA. These SWCNT complexes facilitate the delivery of large biologically active agents through natural barriers within the body, and readily into PBMC. Ensysce has also shown the complexes can be formulated to control relative tissue distribution following intravenous administration. Oligonucleotide delivery especially to PBMCs has been a focus of intense research for years and as seen with the CART therapy is currently limited to in vitro methods using viral vectors or mechanical electroporation. The ability of SWCNT to enable in vivo transfection of PBMCs would be a significant accomplishment for this field which may lead to novel therapeutic approaches for the CART and crisper technologies. Ensysce has an extensive carbon nanotube-related, worldwide intellectual property portfolio, including IP developed at Rice University by the late Nobel Prize winner Dr Richard Smalley as well as from the University of Florida and Trinity College in Dublin. Ensysce was recently issued a US patent to extend its intellectual property coverage for the use of SWCNT for therapeutic applications.

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