DoE-based development of celecoxib loaded PLGA nanoparticles: In ovo assessment of its antiangiogenic effect.

Abnormal angiogenesis plays a main role in the pathogenesis of many diseases such as cancer, and inflammatory autoimmune disorders among others, and its inhibition represents a potential strategy for their management. Celecoxib (CXB) that is one of the most prescribed selective COX-2 inhibitors and is currently approved for the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis inhibits angiogenesis. The objective of this manuscript was to design, develop, and characterize polymeric nanoparticles for the parenteral administration of CXB which the aim of facilitating its administration and improving its antiangiogenic activity while decreasing its adverse effects. A Plackett-Burman design was used to optimize the formulation. The PVA concentration, the sonication time, the sonicator amplitude and the CXB:PLGA ratio were selected as independent variables and particle size, polydispersity index, drug loading, and entrapment efficiency as responses. Optimized nanoparticles (formulations F2, F6 and F9) showed a particle size around 280 nm, a low polydispersion (PDI ≤ 0.2), a negative zeta potential around -25 mV, a high entrapment efficiency (above 88 %) and a controlled drug release for at least 10 days. Moreover, they were physically and chemically stable for at least 3 months when stored at 4 °C. Interestingly, CXB-loaded nanoparticles showed a higher angiogenesis inhibition than CXB in solution administered at the same concentration. F9 nanoparticles that were prepared using PVA at 0.5 %, a sonication time of 7 min, a sonicator amplitude of 80 % and a CXB:PLGA ratio of 20:100 were selected as the most suitable CXB-formulation. It represents a promising strategy to administer CXB and improve its efficacy in disorders with pathological angiogenesis such as cancer and arthritic diseases.

Limitations and Challenges in the Stability of Cysteamine Eye Drop Compounded Formulations.

Accumulation of cystine crystals in the cornea of patients suffering from cystinosis is considered pathognomonic and can lead to severe ocular complications. Cysteamine eye drop compounded formulations, commonly prepared by hospital pharmacy services, are meant to diminish the build-up of corneal cystine crystals. The objective of this work was to analyze whether the shelf life proposed for six formulations prepared following different protocols used in hospital pharmacies is adequate to guarantee the quality and efficacy of cysteamine eye drops. The long-term and in-use stabilities of these preparations were studied using different parameters: content of cysteamine and its main degradation product cystamine; appearance, color and odor; pH and viscosity; and microbiological analysis. The results obtained show that degradation of cysteamine was between 20% and 50% after one month of storage in the long-term stability study and between 35% and 60% in the in-use study. These data confirm that cysteamine is a very unstable molecule in aqueous solution, the presence of oxygen being the main degradation factor. Saturation with nitrogen gas of the solutions offers a means of reducing cysteamine degradation. Overall, all the formulae studied presented high instability at the end of their shelf life, suggesting that their clinical efficacy might be dramatically compromised.

Active Targeted Nanoformulations via Folate Receptors: State of the Art and Future Perspectives.

In normal tissues, the expression of folate receptors is low and limited to cells that are important for embryonic development or for folate reabsorption. However, in several pathological conditions some cells, such as cancer cells and activated macrophages, overexpress folate receptors (FRs). This overexpression makes them a potential therapeutic target in the treatment of cancer and inflammatory diseases to obtain a selective delivery of drugs at altered cells level, and thus to improve the therapeutic efficacy and decrease the systemic toxicity of the pharmacological treatments. Two strategies have been used to achieve this folate receptor targeting: (i) the use of ligands with high affinity to FRs (e.g., folic acid or anti-FRs monoclonal antibodies) linked to the therapeutic agents or (ii) the use of nanocarriers whose surface is decorated with these ligands and in which the drug is encapsulated. This manuscript analyzes the use of FRs as a target to develop new therapeutic tools in the treatment of cancer and inflammatory diseases with an emphasis on the nanoformulations that have been developed for both therapeutic and imaging purposes.