(W1030-03-16) Preparation of ZnO Nanoparticles/Doxorubicin Loaded PLLA Nanofiberous Patch for Tissue Restoration and Immunotherapy in Breast Cancer

Purpose: Breast cancer is the second most common cancer type worldwide. It represents the highest incidence of tumors in women, affecting 13% of them approximately ¹. Doxorubicin is a commonly known chemotherapy used in the treatment of various cancer types, particularly breast cancer. However, previous research studies have proven the possibility of heart damage incidence in patients receiving Doxorubicin. Hence, a localized delivery system for administering Doxorubicin is highly desiranle².

Methods: In this study, both ZnO and Dox nanoformulations had been prepared and assessed for their anticancer activity before being incorporated into PLLA nanofibers matrices using electrospinning technique to form an implantable patch. Then the fabricated patch was assessed for investigating its morphology, physicochemical features, anti-cancer activity as well as tissue restoration ability.

Results: Optimized nanocarriers were prepared then incorporated successfully within PLLA nanofiberous matrices Both unloaded and loaded PLLA nanofiberous matrices were prepared using electrospinning as shown in SEM images demonstrated in Figure 1a and Figure 1b, respectively. Successful incorporation of nanocarriers within PLLA nanofibers has been detected using TEM as shown in Figure 2. Biodegradability test showed that the developed implant loses less than 25% of its initial weight within 30 days as shown in Figure 3a. This confirms their high durability to be able to act as a sustainable drug release implant for up to four month duration. Furthermore, swellability test demonstrates that the patch could reach its maximum swellability within only 3 – 4 days a shown in Figure 3b. Hence, the developed patch can act as controlled release carrier. Finally, cytotoxicity using human fibroblasts confirmed the high biocompatibility of the developed nanofiberous patch. Additionally, they successfully stimulated cell propagation and regeneration 1.5 folds compared to the control (cells only with no tested material).

Conclusion: The developed nanofiberous patch can be used as implantable sustained and controlled release dosage form to prevent cancer recurrence as well as restore damages or lost tissues after breast cancer surgeries.

References: (1) Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2020:70(1): 7-30.
(2) Wolinsky JB, Colson YL, Grinstaff MW. J Control Release. 2012:159(1): 14-16.

Acknowledgements: This work was supported by a grant Science, Technology & Innovation Funding Authority, Egypt, Project No. 45769.

Figure 1. a) PLLA nanofibers, and b) Loaded PLLA Nanofibers

Figure 2. TEM image of Loaded PLLA Nanofibers

Figure 3. a) Biodegradability and b) Swellability of Plain and Loaded Nanofibers