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- Synergistic effect of aloe vera hydrogels with imatinib for pH-responsive drug release in breast cancer treatmentPublication . Khan, Aroob Hasan; Shehzad, Adeeb; Pirela, Paola; Atalaia, Mariana; Ruivinho, Beatriz Lourenço; Rashan, Luay; Miran, Waheed; Duarte, Sofia O. D.; Fonte, PedroImatinib (IM) efficacy as a cancer drug is limited by pharmacokinetic drug resistance developed during systemic circulation before reaching the target site.Hydrogels have attracted attention because of their characteristic physiochemical and biochemical properties, flexibility, and the ability to release drugs directly at target sites causing cancer mitigation. The current study aims at developing Aloe Vera (AV) hydrogels for the efficient and targeted delivery of IM into cancer cells and studying its synergistic effect. Incorporating Aloe Vera into the previously studied Sodium Alginate (SA)/PolyVinyl Alcohol (PVA) hydrogels and loading with IM is expected to reach a pH-responsive release efficiency, enhanced biochemical properties and increased cancer cell cytotoxicity. The hydrogels, SA/PVA and SA/PVA/AV were characterized (FT-IR, SEM) and investigated for their physiochemical properties. The presence of AV and IM were confirmed by the increase in the intensity of band from 3000 to 3500 cm-1, while an increase in the pore size was observed upon the loading of IM. The final formulation, SA/PVA/AV hydrogels displayed increased pore size which leveraged their swelling, degradation, encapsulation, and release properties by 400%, 100%, 56%, and 94%, respectively. The in vitro analysis on breast cancer cells showed that the SA/PVA/AV hydrogels loaded with IM worked synergistically to significantly reduce the cancer cell viability to 40%, surpassing the efficacy of the SA/PVA/AV hydrogel and IM treatments alone. This study highlights the promising potential for the use of AV in the development of a drug delivery system (DDS) for targeting and improving therapeutic outcomes in cancer treatment.
- Inhalable N-acetylcysteine-loaded lactose-coated PLGA nanoparticles for tuberculosis treatmentPublication . Chaudhary, Kabi Raj; Mestre Viegas, Cláudia Sofia; Pirela, Paola; Atalaia, Mariana; Ruivinho, Beatriz Lourenço; Arora, Sanchit; Singh, Arti; Brandão, Pedro; Singh, Charan; Fonte, PedroObjective Glutathione (GSH), known for having mucolytic, anti-inflammatory, and antioxidant activities, is used in clinical practice in several pathologies, including tuberculosis (TB). N-acetylcysteine (NAC) has been primarily used to treat lung conditions and paracetamol-induced liver toxicity. However, NAC exhibits potential antimycobacterial activity through several mechanisms including immunomodulation, enhancement of GSH levels, and direct antimycobacterial effect. In this work, we aim to develop an effective drug delivery system for NAC for inhalable formulations. Methods Herein, we report the development of lactose-coated NAC-loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NAC-PLGA NPs) obtained by double emulsion methodology. Lactose has a double role, as a cryoprotectant agent and dispersant for inhalable formulations. The physicochemical properties of lactose-coated NAC-PLGA NPs were examined in terms of particle size, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency, and morphology. The in vitro release and lung deposition studies were assessed. Results The physicochemical characterization studies revealed the compatibility of the drug with the selected excipients. Moreover, lactose-coated NAC-PLGA NPs showed particle size of 310±3 nm, PdI of 0.15±0.01, and of -11.5±0.4 mV. The in vitro release study suggested a biphasic release profile. Likewise, in vitro lung deposition studies revealed desirable lung deposition parameters, indicating effective particle size for efficient pulmonary delivery. Additionally, in vitro studies for antimycobacterial activity exhibited superior antibacterial activity against Mycobacterium Tuberculosis (MTB) H37Rv. Conclusions These preliminary findings suggest that lactose-coated NAC-PLGA NPs can open the door to new therapeutic options against one of the most drug-refractory and drug-resistant infectious diseases, TB.