During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.

Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsifying drug delivery system (SMEDDS). Based on the solubilities of RLX, Capryol 90, Tween 80/Labrasol ALF, and polyethylene glycol 400 (PEG-400) were selected as the oil, surfactant mixture, and cosurfactant, respectively. Pseudo-ternary phase diagrams were constructed to determine the optimal composition (Capryol 90/Tween 80/Labrasol ALF/PEG-400 in 150/478.1/159.4/212.5 volume ratio) for RLX-SMEDDS with a small droplet size (147.1 nm) and stable microemulsification (PDI: 0.227). Differential scanning calorimetry and powder X-ray diffraction of lyophilized RLX-SMEDDS revealed the loss of crystallinity, suggesting a molecularly dissolved or amorphous state of RLX in the SMEDDS formulation. Moreover, RLX-SMEDDS exhibited significantly higher saturation solubility and dissolution rate in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) than RLX powder. Additionally, oral administration of RLX-SMEDDS to female rats resulted in 1.94- and 1.80-fold higher area under the curve and maximum plasma concentration, respectively, than the RLX dispersion. Collectively, our findings suggest SMEDDS is a promising oral formulation to enhance the therapeutic efficacy of RLX.