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1.
Eur J Pharm Sci ; 102: 188-195, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28300611

ABSTRACT

In recent years, the demand and interest for functionalized polymers have increased for drug delivery purposes. Because of the increased interest, methods that can be used to predict physical and chemical properties of polymers prior to synthesis would be of high value for the design and development of novel polymer structures. Through use of molecular descriptors and Principal Component Analysis, this study explores the possibilities of using in silico methods for polymer design and characterization for property prediction. The results presented in this paper suggest that it is possible to produce a model, which can successfully distinguish between a set of both structurally similar and different polymers based on their surface properties.


Subject(s)
Drug Discovery , Polymers/chemistry , Computer Simulation , Principal Component Analysis , Surface Properties
2.
J Control Release ; 203: 16-22, 2015 Apr 10.
Article in English | MEDLINE | ID: mdl-25660830

ABSTRACT

The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In preclinical and clinical studies adjuvants based on mineral oils (such as incomplete Freund's adjuvant (IFA) and Montanide) are used to create a sustained release depot at the injection site. While the depot effect of mineral oils is important for induction of robust immune responses, their administration is accompanied with severe adverse and long lasting side effects. In order to develop an alternative for IFA family of adjuvants, polymeric nanoparticles (NPs) based on hydrophilic polyester (poly(d,l lactic-co-hydroxymethyl glycolic acid) (pLHMGA)) were prepared. These NPs were loaded with a synthetic long peptide (SLP) derived from HPV16 E7 oncoprotein and a toll like receptor 3 (TLR3) ligand (poly IC) by double emulsion solvent evaporation technique. The therapeutic efficacy of the nanoparticulate formulations was compared to that of HPV SLP+poly IC formulated in IFA. Encapsulation of HPV SLP antigen in NPs substantially enhanced the population of HPV-specific CD8+ T cells when combined with poly IC either co-encapsulated with the antigen or in its soluble form. The therapeutic efficacy of NPs containing poly IC in tumor eradication was equivalent to that of the IFA formulation. Importantly, administration of pLHMGA nanoparticles was not associated with adverse effects and therefore these biodegradable nanoparticles are excellent substitutes for IFA in cancer vaccines.


Subject(s)
Cancer Vaccines/administration & dosage , Human papillomavirus 16/immunology , Interferon Inducers/administration & dosage , Papillomavirus E7 Proteins/administration & dosage , Papillomavirus Infections/therapy , Poly I-C/administration & dosage , Uterine Cervical Neoplasms/therapy , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , Amino Acid Sequence , Animals , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Cell Line, Tumor , Cervix Uteri/virology , Female , Freund's Adjuvant/administration & dosage , Freund's Adjuvant/immunology , Freund's Adjuvant/therapeutic use , Humans , Interferon Inducers/immunology , Interferon Inducers/therapeutic use , Mice, Inbred C57BL , Molecular Sequence Data , Nanoparticles/chemistry , Papillomavirus E7 Proteins/chemistry , Papillomavirus E7 Proteins/immunology , Papillomavirus E7 Proteins/therapeutic use , Papillomavirus Infections/immunology , Poly I-C/immunology , Poly I-C/therapeutic use , Polyesters/chemistry , Uterine Cervical Neoplasms/immunology , Vaccination
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