Browsing by Author "Fonte, Pedro"
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- A brief overview of the oral delivery of insulin as an alternative to the parenteral deliveryPublication . Macedo, Ana; Filipe, Patricia; Thome, Natalia G.; Vieira, Joao; Oliveira, Carolina; Teodosio, Catarina; Ferreira, Raquel; Roque, Luis; Fonte, PedroDiabetes mellitus greatly affects the quality of life of patients and has a worldwide prevalence. Insulin is the most commonly used drug to treat diabetic patients and is usually administered through the subcutaneous route. However, this route of administration is ineffective due to the low concentration of insulin at the site of action. This route of administration causes discomfort to the patient and increases the risk of infection due to skin barrier disturbance caused by the needle. The oral administration of insulin has been proposed to surpass the disadvantages of subcutaneous administration. In this review, we give an overview of the strategies to deliver insulin by the oral route, from insulin conjugation to encapsulation into nanoparticles. These strategies are still under development to attain efficacy and effectiveness that are expected to be achieved in the near future.
- Advances in Pancreatic Cancer treatment by Nano-Based drug delivery systemsPublication . Viegas, Cláudia; Patrício, Ana B.; Prata, João; Fonseca, Leonor; Macedo, Ana S.; Duarte, Sofia O. D.; Fonte, PedroPancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.
- An insight on lipid nanoparticles for therapeutic proteins deliveryPublication . Viegas, Cláudia; Seck, Fatumata; Fonte, PedroTherapeutic proteins are well-tolerated bioactive compounds used in different therapies, due to its high speci-ficity and biopotency. Nevertheless, they may also present some physicochemical instability, leading to loss of bioactivity hampering treatments. This can be avoided by its loading into lipid nanoparticles, which are biocompatible and biodegradable carriers. The use of lipids nanoparticles to deliver therapeutic proteins over-comes different challenges, allowing its administration by all delivery routes. Thus, therapeutic proteins may be loaded into liposomes, the first developed lipid-based nanocarriers composed of phospholipid bilayers, solid lipid nanoparticles composed of a solid lipid matrix, or nanostructured lipid carriers made of a blend of liquid and solid lipid as matrix. The latter are currently marking the trend in lipid nanocarriers due to its high loading capacity, good stability upon storage and better sustained release pattern. Production methods must focus both on attaining the desired nanocarrier features, and maintenance of therapeutic proteins structure and bioactivity. This review aims to make an insight overview on the application of lipid nanoparticles to deliver therapeutic proteins, showing its potential in different therapies. A special focus is given to the production techniques to obtain therapeutic proteins-loaded lipid nanoparticles.
- An overview on spray-drying of protein-loaded polymeric nanoparticles for dry powder inhalationPublication . Marante, Tânia; Viegas, Cláudia Sofia; Duarte, Inês; Macedo, Ana S.; Fonte, PedroThe delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.
- Anticancer activity of rutin and its combination with ionic liquids on renal cellsPublication . Caparica, Rita; Júlio, Ana; Araújo, Maria Eduarda Machado; Baby, André Rolim; Fonte, Pedro; Costa, João Guilherme; Santos de Almeida, TâniaThe renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin's solubility/loading while allowing the maintenance of rutin's anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs-nanoparticles hybrid systems, allowing controlled drug delivery.
- Camptothecin-loaded mesoporous silica nanoparticles functionalized with CpG oligodeoxynucleotide as a new approach for skin cancer treatmentPublication . Qureshi, Munibah; Viegas, Cláudia; Duarte, Sofia O.D.; Girardi, Michael; Shehzad, Adeeb; Fonte, PedroThe therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion. Importantly, CpG oligodeoxynucleotide (CpG ODN) was attached onto the CS-coated FMSNs to leverage the immunostimulatory properties of CpG ODN, augmenting the chemotherapy's efficacy. The final formulation FMSN-CPT-CS-CpG displayed an average size of 241 nm and PDI of 0.316 with an encapsulation efficiency of 95 %. Comprehensive in vitro and in vivo analyses, including B16F10 cells and DMBA/TPA-induced SCC murine model, demonstrated that the FMSN-CPT-CS-CpG formulation significantly enhanced cytotoxicity against B16F10 cells and induced complete regression in 40 % of the in vivo subjects, surpassing the efficacy of standard CPT and FMSN-CPT treatments. This study highlights the potential of combining chemotherapeutic and immunotherapeutic agents in an NDDS for targeted, efficient skin cancer treatment.
- Chitosan nanoparticles: a versatile platform for biomedical applicationsPublication . Bashir, Showkeen Muzamil; Ahmed Rather, Gulzar; Patrício, Ana; Haq, Zulfiqar; Sheikh, Amir Amin; Shah, Mohd Zahoor ul Haq; Singh, Hemant; Khan, Azmat Alam; Imtiyaz, Sofi; Ahmad, Sheikh Bilal; Nabi, Showket; Rakhshan, Rabia; Hassan, Saqib; Fonte, PedroChitosan is a biodegradable and biocompatible natural polymer that has been extensively explored in recent decades. The Food and Drug Administration has approved chitosan for wound treatment and nutritional use. Furthermore, chitosan has paved the way for advancements in different biomedical applications including as a nanocarrier and tissue-engineering scaffold. Its antibacterial, antioxidant, and haemostatic properties make it an excellent option for wound dressings. Because of its hydrophilic nature, chitosan is an ideal starting material for biocompatible and biodegradable hydrogels. To suit specific application demands, chitosan can be combined with fillers, such as hydroxyapatite, to modify the mechanical characteristics of pH-sensitive hydrogels. Furthermore, the cationic characteristics of chitosan have made it a popular choice for gene delivery and cancer therapy. Thus, the use of chitosan nanoparticles in developing novel drug delivery systems has received special attention. This review aims to provide an overview of chitosan-based nanoparticles, focusing on their versatile properties and different applications in biomedical sciences and engineering.
- Design and synthesis of novel quinic acid derivatives: in vitro cytotoxicity and anticancer effect on glioblastomaPublication . Murugesan, Akshaya; Holmstedt, Suvi; Brown, Kenna C.; Koivuporras, Alisa; Macedo, Ana S.; Nguyen, Nga; Fonte, Pedro; Rijo, Patricia; Yli-Harja, Olli; Candeias, Nuno R.; Kandhavelu, MeenakshisundaramAim: Quinic acid (QA) is a cyclic polyol exhibiting anticancer properties on several cancers. However, potential role of QA-derivatives against glioblastoma is not well established. Methodology & results: Sixteen novel QA-derivatives and QA-16 encapsulated poly (lactic-co-glycolic acid) nanoparticles (QA-16-NPs) were screened for their anti-glioblastoma effect using standard cell and molecular biology methods. Presence of a tertiary hydroxy and silylether groups in the lead compound were identified for the antitumor activity. QA-16 have 90% inhibition with the IC50 of 10.66 mu M and 28.22 mu M for LN229 and SNB19, respectively. The induction of apoptosis is faster with the increased fold change of caspase 3/7 and reactive oxygen species. Conclusion: QA-16 and QA-16-NPs shows similar cytotoxicity effect, providing opportunity to use QA-16 as a potential chemotherapeutic agent.
- Enhanced anticancer activity of Hymenocardia acida stem bark extract loaded into PLGA nanoparticlesPublication . Adedokun, Oluwasegun; Ntungwe, Epole N.; Viegas, Cláudia; Adesina Ayinde, Bunyamin; Barboni, Luciano; Maggi, Filippo; Saraiva, Lucilia; Rijo, Patrícia; Fonte, PedroHymenocardia acida (H. acida) is an African well-known shrub recognized for numerous medicinal properties, including its cancer management potential. The advent of nanotechnology in delivering bioactive medicinal plant extract with poor solubility has improved the drug delivery system, for a better therapeutic value of several drugs from natural origins. This study aimed to evaluate the anticancer properties of H. acida using human lung (H460), breast (MCF-7), and colon (HCT 116) cancer cell lines as well as the production, characterization, and cytotoxicity study of H. acida loaded into PLGA nanoparticles. Benchtop models of Saccharomyces cerevisiae and Raniceps ranninus were used for preliminary toxicity evaluation. Notable cytotoxic activity in benchtop models and human cancer cell lines was observed for H. acida crude extract. The PLGA nanoparticles loading H. acida had a size of about 200 nm and an association efficiency of above 60%, making them suitable to be delivered by different routes. The outcomes from this research showed that H. acida has anticancer activity as claimed from an ethnomedical point of view; however, a loss in activity was noted upon encapsulation, due to the sustained release of the drug.
- Evaluation of the antitumour and antiproliferative effect of Xanthohumol-Loaded PLGA nanoparticles on melanomaPublication . Fonseca, Magda; Macedo, Ana S.; Lima, Sofia A. Costa; Reis, Salette; Soares, Raquel; Fonte, PedroCutaneous melanoma is the deadliest type of skin cancer and current treatment is still inadequate, with low patient survival rates. The polyphenol xanthohumol has been shown to inhibit tumourigenesis and metastasization, however its physicochemical properties restrict its application. In this work, we developed PLGA nanoparticles encapsulating xanthohumol and tested its antiproliferative, antitumour, and migration effect on B16F10, malignant cutaneous melanoma, and RAW 264.7, macrophagic, mouse cell lines. PLGA nanoparticles had a size of 312 ± 41 nm and a PdI of 0.259, while achieving a xanthohumol loading of about 90%. The viability study showed similar cytoxicity between the xanthohumol and xanthohumol-loaded PLGA nanoparticles at 48 h with the IC50 established at 10 µM. Similar antimigration effects were observed for free and the encapsulated xanthohumol. It was also observed that the M1 antitumor phenotype was stimulated on macrophages. The ultimate anti-melanoma effect emerges from an association between the viability, migration and macrophagic phenotype modulation. These results display the remarkable antitumour effect of the xanthohumol-loaded PLGA nanoparticles and are the first advance towards the application of a nanoformulation to deliver xanthohumol to reduce adverse effects by currently employed chemotherapeutics.
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