Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer
Autor: | Rabia Arshad, Maria Hassan Kiani, Ayesha Batool, Gul Shahnaz, Sobia Razzaq, Kainat Nousheen |
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Rok vydání: | 2020 |
Předmět: |
Biocompatibility
Polymers Dispersity Cystamine Administration Oral Excipient Breast Neoplasms 02 engineering and technology Hemolysis Biochemistry Permeability Inhibitory Concentration 50 Surface-Active Agents 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Structural Biology Amphiphile Hyaluronic acid medicine Zeta potential Humans Disulfides Hyaluronic Acid Particle Size Molecular Biology 030304 developmental biology Drug Carriers 0303 health sciences General Medicine Permeation 021001 nanoscience & nanotechnology Drug Liberation Tamoxifen Hyaluronan Receptors Nanomedicine Solubility chemistry Drug Design Drug delivery MCF-7 Cells Biophysics Nanoparticles Emulsions Female Lithocholic Acid Drug Screening Assays Antitumor 0210 nano-technology medicine.drug |
Zdroj: | International Journal of Biological Macromolecules. 152:503-515 |
ISSN: | 0141-8130 |
Popis: | The present study was intended to develop a papain grafted S-protected hyaluronic acid-lithocholic acid co-block (PAP-HA-ss-LCA) polymeric excipient as an amphiphilic muco permeating stabilizer for targeting breast cancer epithelial cells overexpressed with CD44 receptors. The mucopermeating, stabilizing and targeting capability of the PAP-HA-ss-LCA polymeric excipient was investigated by manufacturing tamoxifen (TMX) loaded self-nanoemulsifying drug delivery system (SNEDDS). TMX loaded PAP-HA-ss-LCA incorporated SNEDDS (TMX-PAP-HA-ss-LCA SNEDDS) were characterized for their surface chemistry, drug release, permeation enhancement, biocompatibility and antitumor activity. FTIR spectroscopic analysis showed successful synthesis of PAP-HA-ss-LCA polymer. X-ray diffraction (XRD) showed the amorphous form of TMX inside SNEDDS. The observed hydrodynamic diameter of TMX-PAP-HA-ss-LCA SNEDDS was 367.5 nm. Furthermore, Hyaluronic Acid-based Mucoadhesive Self Nanoemulsifying Drug Delivery System (SNEDDS) of TMX showed homogeneity in synthesis with low polydispersity and negative zeta potential due to stabilization with PAP-HA-ss-LCA polymer. The distinct spherical shape of the nanodroplets was evident by transmission electron microscopy (TEM). In vitro release kinetics indicated approximately >80% release within 48 h under sink conditions. Ex-vivo permeation study displayed 7.11-folds higher permeation of TMX by TMX-PAP-HA-ss-LCA in contrast to pure TMX. The biocompatibility study proved that SNEDDS formulation was safe and compatible against macrophages. In vitro cytotoxicity studies demonstrated that TMX-PAP-HA-ss-LCA SNEDDS could efficiently kill MCF-7 breast cancer cells as compared to the native TMX drug. Systemic toxicity studies proved the non-toxic nature of TMX-PAP-HA-ss-LCA in contrast to pure TMX. Based on these evidences, TMX-PAP-HA-ss-LCA SNEDDS formulation seems to be promising mucopermeating, augmented intracellular uptake with strong targeting potential for anti-proliferative activity. |
Databáze: | OpenAIRE |
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