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Made available in DSpace on 2022-05-01T16:48:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-07-20 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Breast cancer is the commonest cancer among women, with more than 2 million cases per year and a lethality rate of 17.7%. The treatment of breast cancer still being a challenge due to the high heterogeneity of tumor cells. In this scenario, the development of targeted nanosystems for drug delivery has been investigated. Thus, the aim of this study was the development and characterization of folic acid-modified curcumin-loaded liposomes (LIP-CCM-FA) for the treatment of breast cancer. For this purpose, LIP-CCM-FA and unmodified liposomes (LIP-CCM) were developed and characterized in vitro using MCF-7 cells culture in two-dimensional (2D) and three-dimensional (3D) models. LIP-CCM and LIP-CCM-FA showed low particles size (~ 138 nm), narrow polydispersity indexes (~ 0.140), negative zeta potential (~ −13 mV), and high drug encapsulation efficiency (> 73%). Furthermore, LIP-CCM-FA showed a significantly greater cytotoxicity effect when compared with free curcumin and LIP-CCM using 2D and 3D cell culture models. In addition, in vitro cellular uptake assays using 2D and 3D models indicated higher cellular internalization and spheroid penetration of LIP-CCM-FA when compared with free curcumin and LIP-CCM, suggesting the potential of folic acid modification for improving drug internalization in breast cancer cells through its recognition by folate receptors overexpressed. In summary, this novel nanosystem demonstrated a greater in vitro antitumoral effect due to its ability to permeate tissues and be specifically recognized by folate receptors. School of Pharmaceutical Science of Ribeirao Preto University of Sao Paulo (USP) School of Pharmaceutical Science of Sao Paulo State University (UNESP), Sao Paulo School of Pharmaceutical Science of Sao Paulo State University (UNESP), Sao Paulo CAPES: 001

Made available in DSpace on 2021-06-25T10:49:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-20 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Prostate cancer is one of the most frequent neoplasms, associated with high mortality. Some factors may intensify its aggressiveness, for example, the overexpression of the epidermal growth factor receptor (EGFR) in some subtypes of prostate tumors. In this context, the inhibition of EGFR helps to fight neoplasia, with the use of the chimeric anti-EGFR monoclonal antibody, cetuximab (CTX). For cancer treatment in the metastatic stage, chemotherapy using docetaxel (DTX) is widely employed, however the drug is very liposoluble, hampering its bioavailability. In this sense, liquid crystalline systems have great potential for the delivery of DTX. Particularly, liquid crystalline nanodispersions can be used in parenteral routes, with many advantages, including the possibility of prolonged drug release, improved pharmacokinetics, allowing passive tumor accumulation by the EPR effect. Thus, the objective of this work was to develop a liquid crystalline nanodispersion (LCN) based on ethoxylated cetyl alcohol 20 and propoxylated 5 as surfactant (Procetyl®), oleic acid, DSPE-PEG-MAL (anchor for CTX binding) and soy phosphatidylcholine as oily phase and 1.5 % poloxamer dispersion in PBS buffer as an aqueous phase. The formulation was loaded with DTX and covalently functionalized with CTX to evaluate its cytotoxic potential against prostate cancer cells. The results suggested that the obtained system has a predominantly hexagonal crystalline phase, was able to be nanodispersed with low polydispersity, and presented negative zeta potential. CTX did not have its structure compromised after thiolation and was successfully covalently linked to LCN. In a prostate cancer cells, PC3, LCNs functionalized with CTX underwent greater cell uptake, resulting in greater cytotoxicity, compared to free DTX and non-functionalized DTX-loaded LCNs. Therefore, the present study reports for the first time an EGFR-targeted liquid crystal nanodispersion for selective to deliver DTX to prostate cells School of Pharmaceutical Sciences of Araraquara São Paulo State University UNESP Department of Drugs and Medicines Federal University of Ceará College of Pharmacy Dentistry and Nursing Department of Pharmacy University of International Integration of the Afro-Brazilian Lusophony Institute of Health Sciences São Carlos Institute of Chemistry University of São Paulo, São Carlos School of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo Ribeirão Preto School of Pharmaceutical Sciences of Araraquara São Paulo State University UNESP Department of Drugs and Medicines CNPq: # 465687/2014-8 FAPESP: #2014/50928-2

The aim of this study was to develop a formulation, containing the propolis standardized extract (EPP-AF®), which can assist in the healing of skin lesions. To achieve this objective the antimicrobial activity and chemical composition of the propolis extract was determined. The final product was subjected to in vitro and in vivo pre-clinical evaluation. The broth macrodilution method was used to determine the antimicrobial activity of the extracts and formulations against the microorganisms most commonly found in burns, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis. Wistar rats with puncture wounded skin were used to evaluate the wound healing properties of propolis. The results of chemical and biological characterization demonstrated the batch-to-batch reproducibility of the standardized extract which is an unprecedented result. The antimicrobial and wound healing activity of the pharmaceutical studied showed the best results when samples contain 3.6% propolis, suggesting that this is the most promising composition.

Made available in DSpace on 2013-08-28T14:07:38Z (GMT). No. of bitstreams: 1 WOS000303805500008.pdf: 934790 bytes, checksum: 5129f2b95886d191ecd3dd83b9c749e6 (MD5) Made available in DSpace on 2013-09-30T19:23:17Z (GMT). No. of bitstreams: 2 WOS000303805500008.pdf: 934790 bytes, checksum: 5129f2b95886d191ecd3dd83b9c749e6 (MD5) WOS000303805500008.pdf.txt: 46028 bytes, checksum: c7220368485f95a3f2bf0d5b66f60ddb (MD5) Previous issue date: 2012-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:34:08Z No. of bitstreams: 2 WOS000303805500008.pdf: 934790 bytes, checksum: 5129f2b95886d191ecd3dd83b9c749e6 (MD5) WOS000303805500008.pdf.txt: 46028 bytes, checksum: c7220368485f95a3f2bf0d5b66f60ddb (MD5) Made available in DSpace on 2014-05-20T15:34:08Z (GMT). No. of bitstreams: 2 WOS000303805500008.pdf: 934790 bytes, checksum: 5129f2b95886d191ecd3dd83b9c749e6 (MD5) WOS000303805500008.pdf.txt: 46028 bytes, checksum: c7220368485f95a3f2bf0d5b66f60ddb (MD5) Previous issue date: 2012-01-01 The aim of this study was to develop a formulation, containing the propolis standardized extract (EPP-AF (R)), which can assist in the healing of skin lesions. To achieve this objective the antimicrobial activity and chemical composition of the propolis extract was determined. The final product was subjected to in vitro and in vivo pre-clinical evaluation. The broth macrodi-lution method was used to determine the antimicrobial activity of the extracts and formulations against the microorganisms most commonly found in burns, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis. Wistar rats with puncture wounded skin were used to evaluate the wound healing properties of propolis. The results of chemical and biological characterization demonstrated the batch-to-batch reproducibility of the standardized extract which is an unprecedented result. The antimicrobial and wound healing activity of the pharmaceutical studied showed the best results when samples contain 3.6% propolis, suggesting that this is the most promising composition. Univ São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, Lab Tecnol Farmaceut, BR-14043903 Ribeirao Preto, SP, Brazil Apis Flora Indl Coml Ltda, Lab Pesquisa Desenvolvimento & Inovacao, BR-14020670 Ribeirao Preto, SP, Brazil Univ Estadual Paulista, Inst Quim, BR-14800900 Araraquara, SP, Brazil Univ Estadual Paulista, Inst Quim, BR-14800900 Araraquara, SP, Brazil

Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

Micropartículas de carboximetilcelulose (CMC)/quitosana contendo vitamina E foram preparadas pelo método de coacervação complexa e seu uso potencial como um sistema de liberação tópico foi avaliado. Estudos da morfologia, da distribuição do tamanho de partículas, da eficiência de encapsulação, da estabilidade física e química e da liberação e permeação cutânea in vitro foram realizados. As análises por Microscopia Eletrônica de Varredura mostraram que as partículas são esféricas, possuem uma superfície homogênea e ausência de agregados, com diâmetros na faixa de 2,7 a 7,6 µm. A eficiência de encapsulação da vitamina E foi 81%. Os estudos de estabilidade química mostraram proteção da vitamina E encapsulada, sendo que a diferença em relação à quantidade de ativo remanescente na emulsão O/A foi de 8,1% e na A/O, de 10,8%, após armazenamento a 45 °C por um período de 60 dias. O ensaio de liberação in vitro mostrou que 48% da vitamina E encapsulada, quantificada por CLAE, foram liberadas em 24 horas de experimento. Nos estudos de retenção e permeação in vitro observou-se que a emulsão A/O proporcionou maior penetração da vitamina E tanto da forma livre como encapsulada.Os sistemas avaliados parecem ser promissores para veiculação de ativos em preparações de uso tópico. Carboxymethylcellulose (CMC)/chitosan microparticles containing vitamin E were prepared by a complex coacervation method and their potential use as a topical delivery system was evaluated. Morphology, particle size distribution, encapsulation yield, physical and chemical stability, in vitro release and permeation through skin were studied. The microparticles appeared to be spherical, with a homogeneous surface and were not aggregated. Mean diameters ranged from 2.7 to 7.6 µm and the encapsulation yield was 81%. Chemical stability studies indicated a protection of encapsulated vitamin E, of 8.1% for O/W and of 10.83% for W/O emulsions, following storage at 45 °C for 60 days. Forty-eight% of vitamin E, determined by HPLC, were released within 24 hours. In vitro permeation and retention studies showed a higher penetration rate of vitamin E in the free and encapsulated forms, from the W/O emulsion. The carriers studied seem to be promising systems for topical administration.

Background Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers. Methods SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. Results Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution. Conclusions The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.