Design-of-Experiment-Assisted Fabrication of Biodegradable Polymeric Nanoparticles: In Vitro Characterization, Biological Activity, and In Vivo Assessment

Abstract

Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER–ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER–ALG/CHS-NP surface was grafted with folic acid (BER–ALG/CHS-NPs–F) for specific targeting in breast cancer. BER–ALG/CHS-NPs–F was optimized by applying the Box–Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER–ALG/CHS-NPs–F was 5.5-fold higher than that of BER–suspension. The antioxidant capacities of BER–ALG/CHS-NPs–F vs BER–suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER–suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER–ALG/CHS-NPs–F toward breast cancer.

Improving the Antimicrobial Potency of Berberine for Endodontic Canal Irrigation Using Polymeric Nanoparticles

“…In the same experimental setup, free BBR inhibited both planktonic and sessile populations, although at significantly higher levels, i.e., ≥125 μg/mL, compared to that accomplished by the BBR-loaded nanoparticles. The need of higher doses of free BBR might suggest the relevance of antibacterial surface-mediated mechanisms as observed before [ 63 ] which may be further supported by the low cellular availability of this molecule [ 67 ].…”

“…As such, planktonic E. faecalis and C. albicans were highly susceptible to BBR-loaded nanoparticles. BBR is reported to act via multiple and dose-dependent mechanisms encompassing intracellular and surface effects targeting specific and/or nonspecific entities or events [ 63 ]. The high activity in the planktonic pathogens might be associated with an easy cellular diffusion of the loaded nanoparticles with subsequent BBR release accomplishing inhibitory effects in microbial intracellular key mechanisms.…”

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs

“…Ding L et al 72 discovered that perfluorocarbon nanoemulsions, compared to poly-cationic/small interfering RNA (siRNA) complexes, demonstrated a more robust inhibition of pancreatic tumor growth due to the enhanced permeability and retention (EPR) effect, suggesting a promising future in the controlled therapy of pancreatic cancer.③Improved Patient Compliance: The liquid form of nanoemulsions facilitates multiple administration routes, including oral, intravenous, and topical applications. Niu Z et al 73 found that nanoemulsion-based delivery of Coenzyme Q10 showed 1.8 to 2.8 times higher bioavailability when administered orally, compared to other mediums, highlighting the potential of nanoemulsions as oral drug carriers (refer to Figure 2 ).④Taste Masking: Nanoemulsions can conceal the bitter taste of oils and drugs, making them more palatable when used as oral drug carriers. 71 ⑤Stability: Nanoemulsions are less prone to issues like flocculation, creaming, and sedimentation.…”