Nanoemulsion Blood-Brain Barrier BBB Considerations and Impact

CBD Nanoemulsion Containing Tween 80: A Safe and Neuroprotective Approach: A Short Critical Analysis 

CBD's Protective Role for Blood Brain Barrier (BBB) and Brain Integrity 

CBD has a well-documented neuroprotective role, supported by its anti-inflammatory, antioxidative, and immunomodulatory effects. It helps maintain BBB integrity by reducing oxidative stress and inflammation, preserving tight junctions between endothelial cells, and preventing leukocyte infiltration into the brain. Experimental studies have shown that CBD modulates chemokines, adhesion molecules, and pro-inflammatory cytokines, which are critical in maintaining the BBB under pathological conditions. Additionally, CBD’s interaction with PPARγ and 5-HT1A receptors contributes to its ability to reduce ischemic damage to the BBB and protect against neuroinflammation. (1) 

Safety Profile of Tween 80 in BBB and Brain Toxicity 

Tween 80 (Polysorbate 80) is a widely used surfactant in pharmaceutical formulations, including nanoemulsions, due to its excellent emulsification properties and safety profile. Key points supporting its non-toxicity are: 

Literature indicates that orally administered Tween 80 exhibits minimal absorption, with approximately 91% being excreted unchanged in feces, highlighting its low systemic bioavailability through the oral route. As a result, oral and subcutaneous administration allow low systemic absorption of Tween 80 to cross the BBB, and minimizing the risk of neurotoxicity (2). From previous research studies, it can be concluded that routes such as intravenous (IV) and intranasal administration are more likely to allow Tween 80 to reach the BBB in relatively high concentrations compared to oral routes (3-9). 

In vivo studies have shown that Tween 80 is efficiently hydrolyzed by esterases in the digestive tract following oral administration (10,11). The fatty acids produced by the hydrolysis of Tween 80 are absorbed from the gastrointestinal tract and further metabolized via beta-oxidation, resulting in the formation of carbon dioxide, which is subsequently exhaled. Polyoxyethylene sorbitan, a byproduct of Tween 80 hydrolysis, is excreted through urine and faeces (12). The absorption of polyoxyethylene sorbitan in the digestive tract has been found to be very low, with approximately 87% of Tween 20 and 91% of Tween 80 being excreted in the faeces (11). 

Even at very high doses, negligible systemic toxicity was observed when PS 80 was orally administered to rats at 22 g/kg body weight. Furthermore, no liver or kidney dysfunction was reported in these studies (13). From another important previous research, it is noteworthy that Tween 80 in a pure aqueous solution is twice as cytotoxic compared to when it is mixed with oil. In our formulation, Tween 80 is combined with oil, which significantly reduces its cytotoxicity, making it far less toxic than its aqueous counterpart (14). 

Tween 80 has been widely recognized as a safe and non-irritant additive in food and pharmaceuticals (15). However, rare cases of hypersensitivity (16) and hepatotoxicity (17) have been reported, but only at very high doses. The Joint Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) Expert Committee on Food Additives has established an acceptable oral daily intake Tween 80 at 25 mg/kg for adults (13,18). 

Importantly, in our formulation, the possible daily intake of Tween 80 remains well below the toxic threshold and within established safe limits, ensuring its safety for use. 

Conclusion 

The formulation combining CBD and Tween 80 demonstrates a robust safety profile and significant therapeutic potential for maintaining Blood-Brain Barrier (BBB) integrity and protecting brain health. CBD’s well-documented neuroprotective effects, including its anti-inflammatory, antioxidative, and immunomodulatory properties, support its role in preserving BBB function. By reducing oxidative stress and inflammation, CBD actively maintains tight junctions and prevents leukocyte infiltration into the brain, offering promising benefits for mitigating neuroinflammation and ischemic damage. 

Tween 80, a widely used surfactant, further enhances the nanoemulsion's stability while maintaining safety. Literature and previous research indicate that orally and subcutaneously administered Tween 80 exhibits minimal absorption, with the majority being excreted in fences, thereby minimizing systemic exposure and reducing the risk of neurotoxicity. Its potential toxicity is only observed in significantly high doses, typically through intravenous or intranasal routes, which are not relevant to this formulation. Moreover, the incorporation of Tween 80 into an oil-based nanoemulsion significantly reduces its cytotoxicity compared to its aqueous form, further enhancing the safety of the product. 

In conclusion, the nanoemulsion formulation, with its well-balanced components and scientifically supported safety and efficacy, is free from risks of BBB or brain damage. Instead, it leverages CBD's protective role and the safe use of Tween 80 to provide a promising, safe therapeutic option for preserving BBB integrity and promoting brain health. 

References 

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