The present invention relates to novel hyaluronic acid (HA) hydrogels comprising vesicles loaded with a drug or a protein or a nucleic acid. The new HA hydrogels provide sustain release formulations that are useful for several clinical and surgical applications, including but not limited to ophthalmology (e.g. glaucoma, corneal, ocular inflammatory, vitreoretinal and medical retinal diseases) and dermatological conditions.