Morphine sulfate nano-controlled release microspheres effectively relieve visceral pain caused by tumor in mice

This work aimed to demonstrate the effect of morphine sulfate nano-controlled release microspheres in relieving tumor-induced visceral pain.

The morphine sulfate nano-controlled release microspheres were prepared and optimized, and their drug release properties in vitro were explored. Chitosan sustained-release microspheres were used to prepare morphine sulfate nanospheres for controlled release. Forty C57BL/6J mice were utilized, divided into a control group (Control, n=10) and a model group (Model, n=30). An intrapancreatic cancer pain model was established using mPA^KPC-luc cells. Mice in the model group were further categorized into the following groups: a blank control group (injected with blank chitosan sustained-release microspheres, Blank, n=10), a Nano + morphine group (injected with morphine-chitosan sustained-release microspheres, Nano + morphine, n=10), and a morphine sulfate group (injected with morphine sulfate, Morphine, n=10). Behavioral assessments were conducted to evaluate pain sensitivity by examining monoamine neurotransmitter levels in the thalamus. Abdominal mechanical allodynia tests and premonition scoring were employed to assess pain perception. Adverse reactions were monitored to evaluate the efficacy and safety profile of morphine sulfate nanospheres.

The cumulative drug release rate in vitro was as high as 99.8% when the amount of crosslinking agent was 8:1. In the Model group, mice exhibited a significant increase in writhing responses due to tumor-induced pain (P < 0.05). Compared to the Blank group, both the Nano + morphine and Morphine groups showed a significant reduction in writhing responses and premonition scores following drug administration (P < 0.05). Additionally, the pain threshold increased (P < 0.05), accompanied by elevation in hypothalamic serotonin (5-HT) levels (P < 0.05) and a decrease in norepinephrine (NE) level (P < 0.05). Furthermore, no significant adverse reactions were observed in these groups.

Morphine sulfate nano-controlled release microspheres exhibit favorable drug release kinetics, demonstrating notable therapeutic efficacy in reliving tumor-induced visceral pain and extending the duration of pain relief. Furthermore, they demonstrate a good safety profile without inducing adverse effects, underscoring their significant clinical value. The results support continued clinical application and promotion of morphine sulfate nano-controlled release microspheres.