Disclosed herein are methods and compositions for sustained release of kappa-opioid agonists. The modified kappa-opioid agonists disclosed herein exhibit high peripheral to CNS selectivity, and benefits patients with visceral and neuropathic pain. In some embodiments, these kappa-opioid agonists of formula I are highly specific for kappa receptors with little or no agonist or antagonist activity to mu or delta receptors. In some embodiments, the kappa-opioid agonists of formula I do not cause CNS-dependent adverse effects. The kappa-opioid agonists of formula I may not cross blood-brain barrier to elicit side effects.
