Cyclosome® Complex

The Bioavailability Bottleneck in Oral Supplementation

One of the most significant challenges in pharmacology and sports nutrition is the oral bioavailability of active compounds. When a supplement is ingested, it must survive the highly acidic environment of the stomach, resist enzymatic degradation in the gastrointestinal tract, and successfully cross the intestinal epithelium. Even if a compound successfully navigates these hurdles, it enters the portal vein and is transported directly to the liver. Here, it is subjected to first-pass metabolism, where hepatic enzymes (such as the cytochrome P450 family) metabolize and often inactivate a large percentage of the compound before it can reach systemic circulation. For highly hydrophobic (water-repelling) compounds, poor aqueous solubility further limits absorption, as they cannot easily dissolve in the aqueous environment of the GI tract to reach the absorptive surfaces of the enterocytes.

Cyclodextrins: The Hydrophobic Solution

To address the issue of poor aqueous solubility, pharmaceutical scientists utilize cyclodextrins (CDs). Cyclodextrins are cyclic oligosaccharides consisting of macrocyclic rings of glucose subunits joined by α-1,4 glycosidic bonds. They possess a unique, truncated cone or toroidal structure. The interior cavity of the cyclodextrin cone is highly hydrophobic, providing a lipophilic microenvironment that can encapsulate hydrophobic drug molecules or supplement compounds. Conversely, the exterior of the cyclodextrin molecule is highly hydrophilic due to the presence of hydroxyl groups. When a hydrophobic compound is entrapped within the cyclodextrin cavity, it forms an 'inclusion complex.' This complex significantly enhances the water solubility of the guest molecule, allowing it to dissolve readily in the aqueous fluids of the digestive tract without altering the molecular structure of the active ingredient itself.

Liposomes: The Phospholipid Shield

While cyclodextrins solve the solubility problem, they do not inherently protect the compound from enzymatic degradation or facilitate specialized cellular uptake. This is where liposomes come into play. Liposomes are spherical vesicles composed of one or more phospholipid bilayers, structurally identical to the lipid bilayers that make up human cell membranes. They feature an aqueous core surrounded by a hydrophobic lipid membrane. Liposomes act as a protective shield, encapsulating the payload and protecting it from the harsh, acidic environment of the stomach and the degradative enzymes of the intestines. Furthermore, because liposomes are made of the same phospholipids as human cell membranes, they can easily fuse with the membranes of enterocytes (intestinal absorptive cells), facilitating the intracellular delivery of their contents.

The Cyclosome® Synergy: A Trojan Horse Delivery

Cyclosome® Technology, developed by Hi-Tech Pharmaceuticals, represents a synergistic convergence of both cyclodextrin and liposomal technologies. In this proprietary process, the hydrophobic active compound is first complexed with cyclodextrin to form a water-soluble inclusion complex. This CD-compound complex is then encapsulated within the aqueous core of a liposome. This creates a 'Trojan Horse' delivery system. The liposome protects the payload through the stomach and facilitates entry into the intestinal cells. Once inside the body, the liposome degrades, releasing the cyclodextrin complex, which keeps the hydrophobic compound soluble and bioavailable in the aqueous environment of the bloodstream until it reaches its target tissue.

Lymphatic Absorption and First-Pass Evasion

Perhaps the most critical pharmacokinetic advantage of the Cyclosome® complex is its ability to circumvent first-pass hepatic metabolism. Standard oral supplements are absorbed into the portal vein and taken straight to the liver. However, highly lipophilic molecules and lipid-based delivery systems like liposomes can be absorbed via the intestinal lymphatic system. In the enterocytes, the liposomal components are packaged into chylomicrons—large lipoprotein particles. These chylomicrons are too large to enter the blood capillaries; instead, they are taken up by the lacteals (lymphatic capillaries) in the intestinal villi. The lymphatic system transports these chylomicrons through the lymphatic vessels, eventually draining directly into the systemic circulation via the thoracic duct, completely bypassing the portal vein and the liver. This lymphatic route prevents the immediate hepatic destruction of the active compounds, resulting in a massively amplified systemic bioavailability and allowing for much lower oral doses to achieve therapeutic or ergogenic effects.

Biological Homonym: The Anaphase-Promoting Complex/Cyclosome (APC/C)

It is crucial to distinguish the proprietary supplement delivery system from the biological entity also known as the 'cyclosome.' In molecular biology, the anaphase-promoting complex/cyclosome (APC/C) is a massive, multi-subunit E3 ubiquitin ligase that plays a vital role in regulating the eukaryotic cell cycle. The APC/C functions by tagging specific cell cycle regulatory proteins with ubiquitin chains, marking them for degradation by the 26S proteasome.

APC/C Mechanism in the Cell Cycle

The primary function of the APC/C is to trigger the transition from metaphase to anaphase during mitosis. It achieves this by targeting two key proteins: securin and cyclin B.

1. Securin Degradation: Securin is an inhibitory protein that binds to and inactivates separase, a protease. When the APC/C (activated by its co-activator Cdc20) ubiquitinates securin, securin is destroyed. This frees separase, which then cleaves cohesin, the protein complex holding sister chromatids together. The cleavage of cohesin allows the sister chromatids to be pulled apart to opposite poles of the cell, initiating anaphase.

2. Cyclin B Degradation: The APC/C also targets cyclin B for destruction. Cyclin B is the regulatory subunit of Maturation Promoting Factor (MPF), which drives the cell into mitosis. The degradation of cyclin B inactivates MPF, allowing the cell to exit mitosis and enter the G1 phase of the next cell cycle.

APC/C as a Therapeutic Target in Oncology

Because the APC/C is essential for cell division, it has become a target of interest in cancer research. Studies, such as those investigating bladder cancer (RT-4 cells), have shown that targeting the APC/C pathway can enhance antiproliferative and apoptotic responses. Small molecule inhibitors like proTAME target the APC/C co-activator Cdc20. By inhibiting the APC/C, these drugs prevent the degradation of securin and cyclin B, causing the cancer cells to arrest in metaphase and ultimately undergo apoptosis (programmed cell death). Research indicates that combining APC/C inhibitors with low doses of traditional chemotherapeutics (like cisplatin and gemcitabine) can significantly increase the Bax/Bcl-2 ratio (promoting apoptosis) and reduce cell colonization ability, offering a promising strategy to improve chemotherapy sensitivity and reduce dose-limiting toxicities.