Optimisation of verapamil hydrochloride loaded polyhydroxyalkanoate nano and microparticles using response surface methodology

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Optimisation of verapamil hydrochloride loaded polyhydroxyalkanoate nano and microparticles using response surface methodology

References

  1. Tan, G. Y. A. et al. Start a research on biopolymer polyhydroxyalkanoate (PHA): A review. Polymers 6, 706–754 (2014).

    Google Scholar 

  2. Mai, J. et al. Synthesis and physical properties of polyhydroxyalkanoate (PHA)-based block copolymers: A review. Int. J. Biol. Macromol. 263, 130204 (2024).

    Google Scholar 

  3. Reddy, V. U. N., Ramanaiah, S. V., Reddy, M. V. & Chang, Y.-C. Review of the developments of bacterial medium-chain-length polyhydroxyalkanoates (mcl-PHAs). Bioengineering 9, 225 (2022).

    Google Scholar 

  4. Paul, V., Pandhi, S., Mahato, D. K., Agarwal, A. & Tripathi, A. D. Polyhydroxyalkanoates (PHAs) and its copolymer nanocarrier application in cancer treatment: An overview and challenges. Int. J. Biol. Macromol. 277, 134201 (2024).

    Google Scholar 

  5. Ben Abdeladhim, R., Reis, J. A., Vieira, A. M. & de Almeida, C. D. Polyhydroxyalkanoates: Medical applications and potential for use in dentistry. Materials 17, 5415 (2024).

    Google Scholar 

  6. Getino, L., Martín, J. L. & Chamizo-Ampudia, A. A review of polyhydroxyalkanoates: Characterization, production, and application from waste. Microorganisms 12, 2028 (2024).

    Google Scholar 

  7. Cendal, A. I. R. et al. Polyhydroxyalkanoate nanoparticles for strategic drug delivery in cartilage tissue engineering. Osteoarthr. Cartil. 32, S290–S291 (2024).

    Google Scholar 

  8. Benedini, L. Polyhydroxyalkanoates based systems: the future of drug delivery and tissue engineering devices. In Bio-Based Nanomaterials (eds. Mishra, A. K. & Hussain, C. M.) 133–169 (Elsevier, Amsterdam, 2022).

  9. Papaneophytou, C., Katsipis, G., Halevas, E. & Pantazaki, A. A. Polyhydroxyalkanoates applications in drug carriers. in Biotechnological Applications of Polyhydroxyalkanoates (ed. Kalia, V. C.) 77–124 (Springer, Singapore, 2019).

  10. Tang, H. J., Neoh, S. Z. & Sudesh, K. A review on poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)] and genetic modifications that affect its production. Front. Bioeng. Biotechnol. 10, 1057067 (2022).

    Google Scholar 

  11. Eichelbaum, M., Ende, M., Remberg, G., Schomerus, M. & Dengler, H. J. The metabolism of DL-[14C]verapamil in man. Drug Metab. Dispos. 7, 145–148 (1979).

    Google Scholar 

  12. Yousry, C., Amin, M. M., Elshafeey, A. H. & El Gazayerly, O. N. Ultrahigh verapamil-loaded controlled release polymeric beads using superamphiphobic substrate: D-optimal statistical design, in vitro and in vivo performance. Drug Deliv. 25, 1448–1460 (2018).

    Google Scholar 

  13. Herman, A. F. & Santos, C. First-pass effect. NCBI Bookshelf (2025).

  14. Pridgen, E. M., Alexis, F. & Farokhzad, O. C. Polymeric nanoparticle technologies for oral drug delivery. Clin. Gastroenterol. Hepatol. 12, 1605–1610 (2014).

    Google Scholar 

  15. Agrawal, Y. O. et al. Verapamil hydrochloride loaded solid lipid nanoparticles: preparation, optimization, characterisation, and assessment of cardioprotective effect in experimental model of myocardial infarcted rats. Biomed. Pharmacother. 154, 113429 (2022).

    Google Scholar 

  16. Li, Y., Abbaspour, M. R., Grootendorst, P. V., Rauth, A. M. & Wu, X. Y. Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology. Eur. J. Pharm. Biopharm. 94, 170–179 (2015).

    Google Scholar 

  17. Khan, A. A., Abdulbaqi, I. M., Abou Assi, R., Murugaiyah, V. & Darwis, Y. Lyophilized hybrid nanostructured lipid carriers to enhance the cellular uptake of verapamil: statistical optimization and in vitro evaluation. Nanoscale Res. Lett. 13, 323 (2018).

    Google Scholar 

  18. Jawed, S., Sorathiya, A. & Srivastava, A. K. Formulation and evaluation of verapamil loaded hollow microspheres. Int. J. Pharm. Sci. Res. 8, 4213–4221 (2017).

    Google Scholar 

  19. Lakshmanan, M., Foong, C. P., Abe, H. & Sudesh, K. Biosynthesis and characterization of co and ter-polyesters of polyhydroxyalkanoates containing high monomeric fractions of 4-hydroxybutyrate and 5-hydroxyvalerate via a novel PHA synthase. Polym. Degrad. Stab. 163, 122–135 (2019).

    Google Scholar 

  20. Surendran, A. et al. Can polyhydroxyalkanoates be produced efficiently from waste plant and animal oils?. Front. Bioeng. Biotechnol. 8, 169 (2020).

    Google Scholar 

  21. Foong, C. P. et al. A novel and wide substrate specific polyhydroxyalkanoate (PHA) synthase from unculturable bacteria found in mangrove soil. J. Polym. Res. 25, 23 (2017).

    Google Scholar 

  22. Aramvash, A., Moazzeni Zavareh, F. & Gholami Banadkuki, N. Comparison of different solvents for extraction of polyhydroxybutyrate from Cupriavidus necator. Eng. Life Sci. 18, 20–28 (2018).

    Google Scholar 

  23. Iwanaga, S. Biochemical principle of Limulus test for detecting bacterial endotoxins. Proc. Jpn. Acad. Ser. B 83, 110–119 (2007).

    Google Scholar 

  24. Sopyan, I. Y., Gozali, D. O., Kurniawansyah, I. S. & Guntina, R. K. Design-Expert software (DoE): An application tool for optimization in pharmaceutical preparations formulation. Int. J. Appl. Pharm. 14, 55–63 (2022).

    Google Scholar 

  25. Chakraborty, P., Dey, S., Parcha, V., Bhattacharya, S. S. & Ghosh, A. Design expert supported mathematical optimization and predictability study of buccoadhesive pharmaceutical wafers of loratadine. Biomed. Res. Int. 2013, 197398 (2013).

    Google Scholar 

  26. Struzek, A.-M. & Scherließ, R. Quality by design as a tool in the optimisation of nanoparticle preparation—A case study of PLGA nanoparticles. Pharmaceutics 15, 617 (2023).

    Google Scholar 

  27. Narayanan, K., Subrahmanyam, V. M. & Venkata Rao, J. A fractional factorial design to study the effect of process variables on the preparation of hyaluronidase loaded PLGA nanoparticles. Enzyme Res. 2014, 162962 (2014).

    Google Scholar 

  28. Lakshmana Prabu, S., Shirwaikar, A. A., Shirwaikar, A. & Kumar, A. Formulation and evaluation of sustained release microspheres of rosin containing aceclofenac. Ars Pharm. 50, 1–12 (2009).

    Google Scholar 

  29. Sankar, P. R., Snehalatha, K. S., Firdose, S. T. & Babu, P. S. Applications of HPLC in pharmaceutical analysis. Int. J. Pharm. Sci. Rev. Res. 59, 117–124 (2019).

    Google Scholar 

  30. Jain, M. & Shrivastava, S. N. A stability indicating assay method for verapamil tablets by high performance liquid chromatography for stability studies. Anal. Chem. 1, 6–9 (2007).

    Google Scholar 

  31. Madhuri, P. L. & Geetha, V. Development and validation of UV spectrophotometric methods. Asian J. Pharm. Anal. Med. Chem. 2, 134–143 (2016).

    Google Scholar 

  32. Zhang, S., Prabhakaran, M. P., Qin, X. & Ramakrishna, S. Biocomposite scaffolds for bone regeneration: role of chitosan and hydroxyapatite within poly-3-hydroxybutyrate-co-3-hydroxyvalerate on mechanical properties and in vitro evaluation. J. Mech. Behav. Biomed. Mater. 51, 88–98 (2015).

    Google Scholar 

  33. Kaniuk, Ł & Stachewicz, U. Development and advantages of biodegradable PHA polymers based on electrospun PHBV fibers for tissue engineering and other biomedical applications. ACS Biomater. Sci. Eng. 7, 5339–5362 (2021).

    Google Scholar 

  34. Ansari, S., Sami, N., Yasin, D., Ahmad, N. & Fatma, T. Biomedical applications of environmental friendly poly-hydroxyalkanoates. Int. J. Biol. Macromol. 183, 549–563 (2021).

    Google Scholar 

  35. Trakunjae, C. et al. Statistical optimization of P(3HB-co-3HHx) copolymers production by Cupriavidus necator PHB–4/pBBR_CnPro-phaCRp and its properties characterization. Sci. Rep. 13, 9005 (2023).

    Google Scholar 

  36. Tan, F. H. P., Nadir, N. & Sudesh, K. Microalgal biomass as feedstock for bacterial production of PHA: Advances and future prospects. Front. Bioeng. Biotechnol. 10, 879476 (2022).

    Google Scholar 

  37. Dullah, E. C. & Ongkudon, C. M. Current trends in endotoxin detection and analysis of endotoxin-protein interactions. Crit. Rev. Biotechnol. 37, 251–261 (2017).

    Google Scholar 

  38. Sudesh, K., Abe, H. & Doi, Y. Synthesis, structure and properties of polyhydroxyalkanoates: Biological polyesters. Prog. Polym. Sci. 25, 1503–1555 (2000).

    Google Scholar 

  39. Sharma, N., Madan, P. & Lin, S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study. Asian J. Pharm. Sci. 11, 404–416 (2016).

    Google Scholar 

  40. Eslami, M., Nikkhah, S. J., Eslami, E. & Hashemianzadeh, S. M. A new insight into encapsulation process of a drug molecule in the polymer/surfactant system: A molecular simulation study. Struct. Chem. 31, 2051–2062 (2020).

    Google Scholar 

  41. Pagliano, G., Galletti, P., Samorì, C., Zaghini, A. & Torri, C. Recovery of polyhydroxyalkanoates from single and mixed microbial cultures: A review. Front. Bioeng. Biotechnol. 9, 1–28 (2021).

    Google Scholar 

  42. Zambaux, M. F. et al. Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. J. Control. Release 50, 31–40 (1998).

    Google Scholar 

  43. Freiberg, S. & Zhu, X. X. Polymer microspheres for controlled drug release. Int. J. Pharm. 282, 1–18 (2004).

    Google Scholar 

  44. Govender, T., Stolnik, S., Garnett, M. C., Illum, L. & Davis, S. S. PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J. Control. Release 57, 171–185 (1999).

    Google Scholar 

  45. Jain, R. A. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21, 2475–2490 (2000).

    Google Scholar 

  46. Prakash, P., Lee, W. H., Loo, C. Y., Wong, H. S. & Parumasivam, T. Advances in polyhydroxyalkanoate nanocarriers for effective drug delivery: An overview and challenges. Nanomaterials 12, 1–20 (2022).

    Google Scholar 

  47. Lee, K. H., Khan, F. N., Cosby, L., Yang, G. & Winter, J. O. Polymer concentration maximizes encapsulation efficiency in electrohydrodynamic mixing nanoprecipitation. Front. Nanotechnol. 3, 719710 (2021).

    Google Scholar 

  48. Shkodra, B. et al. Effect of surfactant on the size and stability of PLGA nanoparticles encapsulating a protein kinase C inhibitor. Int. J. Pharm. 566, 756–764 (2019).

    Google Scholar 

  49. Garms, B. C. et al. Evaluating the effect of synthesis, isolation, and characterisation variables on reported particle size and dispersity of drug loaded PLGA nanoparticles. Mater. Adv. 2, 5657–5671 (2021).

    Google Scholar 

  50. Ayoub, M. et al. Study of the effect of formulation parameters/variables to control the nanoencapsulation of hydrophilic drug via double emulsion technique. J. Biomed. Nanotechnol. 7, 255–262 (2011).

    Google Scholar 

  51. Ramazani, F. et al. Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges. Int. J. Pharm. 499, 358–367 (2016).

    Google Scholar 

  52. Ding, S., Serra, C. A., Vandamme, T. F., Yu, W. & Anton, N. Double emulsions prepared by two-step emulsification: History, state-of-the-art and perspective. J. Control. Release 295, 31–49 (2019).

    Google Scholar 

  53. Ghazi, N. F., Burley, J. C., Dryden, I. L. & Roberts, C. J. High-throughput microarray approaches for predicting the stability of drug–polymer solid dispersions. Mol. Pharm. 22, 343–362 (2025).

    Google Scholar 

  54. Pilanya, U., Pilaniya, K., Chandrawanshi, H. K., Gupta, N. & Rajput, M. S. Formulation and evaluation of verapamil hydrochloride loaded solid lipid microparticles. Pharmazie 66, 24–30 (2011).

    Google Scholar 

  55. Mosalam, E. M. et al. Enhanced neuroprotective effect of verapamil-loaded hyaluronic acid modified carbon quantum dots in an in-vitro model of amyloid-induced Alzheimer’s disease. Int. J. Biol. Macromol. 275, 133742 (2024).

    Google Scholar 

  56. Faisal, M. M. et al. Verapamil-loaded cubosomes for enhancing intranasal drug delivery: Development, characterization, ex vivo permeation, and brain biodistribution studies. AAPS PharmSciTech 25, 95 (2024).

    Google Scholar 

  57. Moeed, A. et al. Verapamil hydrochloride nanoparticles formulated with chitosan and sodium alginate by an ionic gelation method. Trop. J. Pharm. Res. 20, 1105–1111 (2021).

    Google Scholar 

  58. Qi, S. et al. Insights into the role of polymer-surfactant complexes in drug solubilisation/stabilisation during drug release from solid dispersions. Pharm. Res. 30, 290–302 (2013).

    Google Scholar 

  59. Fischer, K. & Schmidt, M. Pitfalls and novel applications of particle sizing by dynamic light scattering. Biomaterials 98, 79–91 (2016).

    Google Scholar 

  60. Stetefeld, J., McKenna, S. A. & Patel, T. R. Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys. Rev. 8, 409–427 (2016).

    Google Scholar 

  61. Pilaniya, U., Pilaniya, K., Chandrawanshi, H. K., Gupta, N. & Rajput, M. S. Biodegradable solid lipid microparticles loaded with diltiazem hydrochloride for oral delivery: Preparation and in-vitro/in-vivo evaluation. J. Drug Deliv. Ther. 1, 1–6 (2011).

    Google Scholar 

  62. Albanese, A., Tang, P. S. & Chan, W. C. W. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu. Rev. Biomed. Eng. 14, 1–16 (2012).

    Google Scholar 

  63. da Silva, R. Y. P., de Menezes, D. L. B., Oliveira, V. S., Converti, A. & de Lima, Á. A. N. Microparticles in the development and improvement of pharmaceutical formulations: An analysis of in vitro and in vivo studies. Int. J. Mol. Sci. 24, 5441 (2023).

    Google Scholar 

  64. Dowdall, N. & Hoare, T. β-1,3-glucan microparticles and nanoparticles: Fabrication methods and applications in immunomodulation and targeted drug delivery. Adv. Healthc. Mater. 14, 2501006 (2025).

    Google Scholar 

  65. Fisher, J. D., Acharya, A. P. & Little, S. R. Micro and nanoparticle drug delivery systems for preventing allotransplant rejection. Clin. Immunol. 160, 24–35 (2015).

    Google Scholar 

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