.jpg "Research Chemical Sciences")
.png "Research Chemical Sciences")
This is a full breakdown and explanation of the Poly-Cell solvent used in Umbrella Labs SARMS. This is proprietary to Umbrella and is a break though method in making the entire liquid experience not only the most effective but also the most pleasant in terms of taste as well. Read on to find out everything you need to know about the Poly-Cell formula...
Introducing Umbrella Labs’ Poly-Cell FormulaTM SARM solutions
We employ an FDA-approved amphiphilic copolymer + coconut MCT oil to form polymeric micelles that enhance the bioavailability of select SARMs. Furthermore, our nano-emulsification process ensures minimum polymeric micelle size and variance. Most importantly, our Poly-Cell FormulaTM is optimized for sublingual absorption with a minimal taste profile. This stands in contrast to PEG, which is often intolerable for sublingual delivery due to its very unpleasant taste, leading to poor compliance among research participants.
What are polymeric micelles?
Polymeric micelles offer fantastic potential as a drug delivery system for compounds that are hydrophobic and exhibit poor bioavailability which results from the unique core-shell structure. Their inner hydrophobic core enables incorporation of poorly water-soluble drugs or compounds thus improving their stability and bioavailability. Typically, the inner core of the PMs is formed with hydrophobic blocks of the copolymers by hydrophobic interaction. Alternatively, they can also be formed by electrostatic interactions, using charged block copolymers. Our proprietary Poly-Cell FormulaTM uses an amphipathic copolymer in conjunction with medium chain triglycerides from coconut oil. The resulting emulsion absorbs rapidly under the tongue with minimal taste/residue, offering consistent and reliable dosing for research studies.
How do polymeric micelles improve bioavailability of SARMs?
The main mechanisms responsible for the enhancement of drug/compound absorption by polymeric micelles are the following: protection of the drug/compound cargo during mucosal layer transit (for sublingual delivery) or GI tract transit (if swallowed); release of the loaded cargo in a controlled manner; extending time in blood circulation; and inhibition of efflux pumps to improve drug/compound accumulation. Several parameters seem to influence transit of micelles across the epithelial barrier, including surface hydrophobicity, polymer structure, and particle size (ie. smaller sizes cross into the blood stream more easily) (des Rieux et al. 2006). Our nano-emulsification step yields very small particles sizes that enable smaller micelles, thus facilitating easy transit across the epithelial barrier into the blood stream.
The inner layer of polymeric micelles is made up of hydrophobic core, which functions as the “cargo hold” that contains the SARM. The outer shell determines the pharmacokinetic behavior in vivo, while the cargo hold of the inner core is responsible for entrapment/encapsulation (Pathak, Vaidya, and Pandey 2019). The hydrophilic outer shell decreases unwanted drug interactions and ensure that micelles remain in a dispersed state. These polymeric micelles exert the potential of improving bioavailability of hydrophobic compounds, such as most SARMs. They also increase metabolic stability. Notably, the hydrophobic core of the micelle is sterically stabilized and exhibits less opsonization by antibodies and consequently less unwanted uptake by immune system cells. This results in longer circulation time of the encapsulated compound in the blood due to lack of interference from the immune system (Chiappetta and Sosnik 2007).
Another substantial advantage of encapsulation in polymeric micelles is that non-specific binding interactions with blood proteins are reduced due to steric repulsion by the hydrophilic polymer ends surrounding the SARM-encapsulated hydrophobic core. For instance, non-specific binding with serum albumin or lipoprotein, which are abundant in blood, can cause drugs to lose potency because only the unbound fraction exhibits pharmacologic effects (Bohnert and Gan 2013).
What is the advantage of sublingual absorption?
Most SARMs in liquid form are solubilized in polyethylene glycol (PEG), which has a notoriously bad taste. As a result, research participant compliance with sublingual delivery often fails because very few people are willing to tolerate it. In contrast, our Poly-Cell FormulaTM has a minimal taste profile (ie. mild taste with no lingering aftertaste). This improves compliance and reduces the urge to “wash it down” with a beverage, which obviously undermines sublingual absorption. After depositing a dose under the tongue and allowing it to absorb for 1 minute, our Poly-Cell FormulaTM solutions become virtually undetectable.
The most important value proposition of sublingual delivery is that it bypasses first-pass metabolism in the liver. This actually has two main benefits: first, it prevents the destructive metabolism of SARMs that leads to their clearance from the body; second, it prevents the exposure of the liver to a higher initial concentration of SARMs, thus reducing the risk of hepatotoxicity, which is a rare adverse reaction associated with oral SARM use that has been observed in a handful of cases (Flores, Chitturi, and Walker 2020). Thus, sublingual delivery is clearly the superior choice for future clinical trials.
Are there other benefits of amphipathic SARM solutions?
Intriguingly, research has shown that the amphipathic molecules which comprise the core components of our Poly-Cell FormulaTM have two other notable benefits: they help skeletal muscle cells retain their normal mechanical integrity in oxidative environments (ie. during exercise) (Wong et al. 2017), and they promote muscle cell membrane durability (Spurney et al. 2011; Ballas et al. 2004). These benefits are of particular interest to researchers studying the effects of SARMs in the context of anerobic weight-bearing exercise, because of the microscopic tears that occur in muscle fibers during resistance training. This is especially relevant given recent evidence showing that exercise-induced muscle damage is probably not essential for hypertrophy (Wackerhage et al. 2019); rather, cellular mechanosensing and metabolic changes are what ultimately drive muscle growth in response to exercise. Thus, since protecting muscle cells from unnecessary shear stress is likely advantageous to long-term hypertrophic growth, then it is reasonable to hypothesize that delivery of SARMs to muscle cells in polymeric micelles comprised of FDA-approved amphipathic molecules is an added benefit, since they protect the integrity of muscle cell membranes.
This information is for educational purposes only. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).
References
Ballas, Samir K., Beatrice Files, Lori Luchtman-Jones, Lennette Benjamin, Paul Swerdlow, Lee Hilliard, Thomas Coates, Miguel Abboud, Slawomir Wojtowicz-Praga, and J. Michael Grindel. 2004. “Phase I Study of a Non-Ionic Surfactant in the Management of Acute Chest Syndrome.” Hemoglobin. https://doi.org/10.1081/HEM-120035919.
Bohnert, Tonika, and Liang Shang Gan. 2013. “Plasma Protein Binding: From Discovery to Development.” Journal of Pharmaceutical Sciences. https://doi.org/10.1002/jps.23614.
Chiappetta, Diego A., and Alejandro Sosnik. 2007. “Poly(Ethylene Oxide)-Poly(Propylene Oxide) Block Copolymer Micelles as Drug Delivery Agents: Improved Hydrosolubility, Stability and Bioavailability of Drugs.” European Journal of Pharmaceutics and Biopharmaceutics. https://doi.org/10.1016/j.ejpb.2007.03.022.
Flores, Joan Ericka, Shivakumar Chitturi, and Sarah Walker. 2020. “Drug‐Induced Liver Injury by Selective Androgenic Receptor Modulators.” Hepatology Communications. https://doi.org/10.1002/hep4.1456.
Pathak, Chandramani, Foram U. Vaidya, and Shashibhal M. Pandey. 2019. “Mechanism for Development of Nanobased Drug Delivery System.” In Applications of Targeted Nano Drugs and Delivery Systems. https://doi.org/10.1016/b978-0-12-814029-1.00003-x.
Introducing Umbrella Labs’ Poly-Cell FormulaTM SARM solutions
We employ an FDA-approved amphiphilic copolymer + coconut MCT oil to form polymeric micelles that enhance the bioavailability of select SARMs. Furthermore, our nano-emulsification process ensures minimum polymeric micelle size and variance. Most importantly, our Poly-Cell FormulaTM is optimized for sublingual absorption with a minimal taste profile. This stands in contrast to PEG, which is often intolerable for sublingual delivery due to its very unpleasant taste, leading to poor compliance among research participants.
What are polymeric micelles?
Polymeric micelles offer fantastic potential as a drug delivery system for compounds that are hydrophobic and exhibit poor bioavailability which results from the unique core-shell structure. Their inner hydrophobic core enables incorporation of poorly water-soluble drugs or compounds thus improving their stability and bioavailability. Typically, the inner core of the PMs is formed with hydrophobic blocks of the copolymers by hydrophobic interaction. Alternatively, they can also be formed by electrostatic interactions, using charged block copolymers. Our proprietary Poly-Cell FormulaTM uses an amphipathic copolymer in conjunction with medium chain triglycerides from coconut oil. The resulting emulsion absorbs rapidly under the tongue with minimal taste/residue, offering consistent and reliable dosing for research studies.
How do polymeric micelles improve bioavailability of SARMs?
The main mechanisms responsible for the enhancement of drug/compound absorption by polymeric micelles are the following: protection of the drug/compound cargo during mucosal layer transit (for sublingual delivery) or GI tract transit (if swallowed); release of the loaded cargo in a controlled manner; extending time in blood circulation; and inhibition of efflux pumps to improve drug/compound accumulation. Several parameters seem to influence transit of micelles across the epithelial barrier, including surface hydrophobicity, polymer structure, and particle size (ie. smaller sizes cross into the blood stream more easily) (des Rieux et al. 2006). Our nano-emulsification step yields very small particles sizes that enable smaller micelles, thus facilitating easy transit across the epithelial barrier into the blood stream.
The inner layer of polymeric micelles is made up of hydrophobic core, which functions as the “cargo hold” that contains the SARM. The outer shell determines the pharmacokinetic behavior in vivo, while the cargo hold of the inner core is responsible for entrapment/encapsulation (Pathak, Vaidya, and Pandey 2019). The hydrophilic outer shell decreases unwanted drug interactions and ensure that micelles remain in a dispersed state. These polymeric micelles exert the potential of improving bioavailability of hydrophobic compounds, such as most SARMs. They also increase metabolic stability. Notably, the hydrophobic core of the micelle is sterically stabilized and exhibits less opsonization by antibodies and consequently less unwanted uptake by immune system cells. This results in longer circulation time of the encapsulated compound in the blood due to lack of interference from the immune system (Chiappetta and Sosnik 2007).
Another substantial advantage of encapsulation in polymeric micelles is that non-specific binding interactions with blood proteins are reduced due to steric repulsion by the hydrophilic polymer ends surrounding the SARM-encapsulated hydrophobic core. For instance, non-specific binding with serum albumin or lipoprotein, which are abundant in blood, can cause drugs to lose potency because only the unbound fraction exhibits pharmacologic effects (Bohnert and Gan 2013).
What is the advantage of sublingual absorption?
Most SARMs in liquid form are solubilized in polyethylene glycol (PEG), which has a notoriously bad taste. As a result, research participant compliance with sublingual delivery often fails because very few people are willing to tolerate it. In contrast, our Poly-Cell FormulaTM has a minimal taste profile (ie. mild taste with no lingering aftertaste). This improves compliance and reduces the urge to “wash it down” with a beverage, which obviously undermines sublingual absorption. After depositing a dose under the tongue and allowing it to absorb for 1 minute, our Poly-Cell FormulaTM solutions become virtually undetectable.
The most important value proposition of sublingual delivery is that it bypasses first-pass metabolism in the liver. This actually has two main benefits: first, it prevents the destructive metabolism of SARMs that leads to their clearance from the body; second, it prevents the exposure of the liver to a higher initial concentration of SARMs, thus reducing the risk of hepatotoxicity, which is a rare adverse reaction associated with oral SARM use that has been observed in a handful of cases (Flores, Chitturi, and Walker 2020). Thus, sublingual delivery is clearly the superior choice for future clinical trials.
Are there other benefits of amphipathic SARM solutions?
Intriguingly, research has shown that the amphipathic molecules which comprise the core components of our Poly-Cell FormulaTM have two other notable benefits: they help skeletal muscle cells retain their normal mechanical integrity in oxidative environments (ie. during exercise) (Wong et al. 2017), and they promote muscle cell membrane durability (Spurney et al. 2011; Ballas et al. 2004). These benefits are of particular interest to researchers studying the effects of SARMs in the context of anerobic weight-bearing exercise, because of the microscopic tears that occur in muscle fibers during resistance training. This is especially relevant given recent evidence showing that exercise-induced muscle damage is probably not essential for hypertrophy (Wackerhage et al. 2019); rather, cellular mechanosensing and metabolic changes are what ultimately drive muscle growth in response to exercise. Thus, since protecting muscle cells from unnecessary shear stress is likely advantageous to long-term hypertrophic growth, then it is reasonable to hypothesize that delivery of SARMs to muscle cells in polymeric micelles comprised of FDA-approved amphipathic molecules is an added benefit, since they protect the integrity of muscle cell membranes.
This information is for educational purposes only. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).
References
Ballas, Samir K., Beatrice Files, Lori Luchtman-Jones, Lennette Benjamin, Paul Swerdlow, Lee Hilliard, Thomas Coates, Miguel Abboud, Slawomir Wojtowicz-Praga, and J. Michael Grindel. 2004. “Phase I Study of a Non-Ionic Surfactant in the Management of Acute Chest Syndrome.” Hemoglobin. https://doi.org/10.1081/HEM-120035919.
Bohnert, Tonika, and Liang Shang Gan. 2013. “Plasma Protein Binding: From Discovery to Development.” Journal of Pharmaceutical Sciences. https://doi.org/10.1002/jps.23614.
Chiappetta, Diego A., and Alejandro Sosnik. 2007. “Poly(Ethylene Oxide)-Poly(Propylene Oxide) Block Copolymer Micelles as Drug Delivery Agents: Improved Hydrosolubility, Stability and Bioavailability of Drugs.” European Journal of Pharmaceutics and Biopharmaceutics. https://doi.org/10.1016/j.ejpb.2007.03.022.
Flores, Joan Ericka, Shivakumar Chitturi, and Sarah Walker. 2020. “Drug‐Induced Liver Injury by Selective Androgenic Receptor Modulators.” Hepatology Communications. https://doi.org/10.1002/hep4.1456.
Pathak, Chandramani, Foram U. Vaidya, and Shashibhal M. Pandey. 2019. “Mechanism for Development of Nanobased Drug Delivery System.” In Applications of Targeted Nano Drugs and Delivery Systems. https://doi.org/10.1016/b978-0-12-814029-1.00003-x.
