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Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CS L , medium CS M , high CS H molecular weights) and Labrasol ® in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CS M and CS H ; low cationic charge of CS L acted as both electrostatic and steric stabilizer by significant size reduction to 394 nm with charge of 21.5 meV. Solubility of ATR-CS L increased to 60-fold relative to pure ATR and ATR-L. Nanocrystals were characterized for physiochemical properties. Scanning electron microscopy revealed scaffold-like structures with high surface area. X-ray powder diffractometry and differential scanning calorimetry revealed crystalline to slight amorphous state changes after cationic charge size reduction. Fourier transform-infrared spectra indicated no potent drug-excipient interactions. The enhanced dissolution profile of ATR-CS L indicates that sustained release was achieved compared with ATR-L and Lipitor ® . Anti-hyperlipidemic performance was pH dependent where ATR-CS L exhibited 2.5-fold higher efficacy at pH 5 compared to pH 6 and Lipitor ® . Stability studies indicated marked changes in size and charge for ATR-L compared to ATR-CS L exemplifying importance of the stabilizer. Therefore, nanocrystals developed with CS L as a stabilizer is a promising choice to enhance dissolution, stability, and in-vivo efficacy of major Biopharmaceutical Classification System II/IV drugs.