The oral route is the utmost common and preferable route for the delivery of therapeutic agents. It has many advantages over other routes such as high patient compliance, non-invasive, easy of administration, low product cost, and easy manufacturing of orally administered delivery systems [1]. It also provides a high absorption surface area and different cells for absorption like M-cells, goblet cells, and epithelial cells [2].

Herbal bioactive compounds are vital constituents in drug discovery and are used for treating various diseases [3]. The wide therapeutic history and huge chemical diversity of the phytochemicals make them attractive for the treatment of diseases. Many herbal compounds have low bioavailability which limits their clinical application. The low bioavailability is due to poor solubility and poor permeability or a combination of both [4].

Bergenin (BN) is an herbal bioactive compound obtained from various species of Bergenia such as Bergenia ciliate, Bergenia ligulate, and Bergenia stracheyi. Chemically, BN belongs to the polyphenolic category and has several pharmacological activities i.e., antidiabetic, anti-inflammatory, antioxidant, antimicrobial, neuroprotective, antitussive, etc [5]. It has low solubility and low permeability (BCS-IV) and is eradicated through the P-glycoprotein (P-gp) efflux pump, which leads to poor bioavailability [6].

There are various colloidal (10–1000 nm) drug delivery systems stated to increase the therapeutic efficiency and bioavailability of the poorly soluble therapeutic agent such as polymeric nanoparticles of atorvastatin [7], quercetin, and gallic acid [8], solid lipid nanoparticle of ferulic acid [9], and curcumin [10], nanostructured lipid carrier (NLC) of 6-Gingerol (Wei eta l., 2018) and zotepine [11]. In that, NLC is a novel colloidal carrier for the enhancement of bioavailability and therapeutic efficacy of poorly soluble therapeutics. NLC is composed of a blend of physiologically biocompatible and generally recognized as safe (GRAS), solid, liquid lipids, and surfactants [12]. It has several benefits over solid lipid NPs i.e., high drug loading, better stability, extended-release, and low drug expulsion [13,14]. Various research works on NLCs have been reported previously for the enhancement of the therapeutic efficacy of poorly soluble drugs. Soni and co-workers formulated raloxifene-loaded NLC for oral delivery and showed a 4.79-fold higher bioavailability than pure raloxifene [15]. Singh and co-workers formulated exemestane-loaded NLC with 3.9-fold higher oral bioavailability than pure exemestane [16]. Sartaj and co-workers formulated ribociclib-loaded NLC for oral delivery and found 3.54 times higher bioavailability than pure ribociclib dispersion [17]. Several approaches have been reported for the improvement of bioavailable therapeutic efficacy of BN like phospholipid complex solid dispersion [6], inclusion complex using beta-cyclodextrin [18], xanthan gum stabilized silver nanoparticles [19], and albumin nanoparticles [20], etc.

The present study was designed to formulate bergenin-loaded nano-lipid carriers (BNNLCs) for the enhancement of bioavailability and therapeutic efficiency. BNNLCs were prepared by the melt-emulsification and ultrasonication method using selected formulation components and optimized by Box-Behnken design (BBD). The selection of optimized bergenin nanolipid carriers (BNNLCo) was done by point prediction approach. BNNLCo was further evaluated for various physicochemical as well as in vitro parameters. Finally, it was evaluated for in-vivo pharmacokinetic and pharmacodynamic activity.