Abstract
The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the P-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential −14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R2 = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10−fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.
Highlights
Berberine chloride (BBR) is a naturally derived isoquinoline alkaloid found in several medicinal herbs, namely, Berberis aristata, Coptis japonica, Coptis chinensis, Hydrastis canadensis, Phellondendron amurense, and PhellondendronchinenseSchneid [1]
It is suggested that NPs can be formed by enveloping the negatively charged calcium alginate complex in a pregel state with chitosan–cationic polymer, and the pregel state is required to allow the ionic interactions between calcium, alginate, and chitosan to form NPs [21]
Berberine-Loaded Nanoparticles (BNPs) were successfully prepared by the ionic gelation method using P-gp inhibitors chitosan and sodium alginate, which could minimize the efflux of the drug out of the enterocytes
Summary
Berberine chloride (BBR) is a naturally derived isoquinoline alkaloid found in several medicinal herbs, namely, Berberis aristata, Coptis japonica, Coptis chinensis, Hydrastis canadensis, Phellondendron amurense, and PhellondendronchinenseSchneid [1]. It has been primarily recommended for diarrhea and gastroenteritis, including many other biological activities, such as hypoglycemic, hypolipidemic, antiproliferative, antineoplastic, and antiarrhythmic activities [2]. BBR is prepared by chemical synthesis and available in the market as chloride and in sulfate-salt form. BBR is a yellowish crystalline powder with a bitter taste that is either odorless or has a slight odor. Its salt forms are somewhat more soluble [4]
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