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1.
Int J Pharm ; 559: 373-381, 2019 Mar 25.
Article in English | MEDLINE | ID: mdl-30716402

ABSTRACT

Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (PLGA micro-particles), containing a model antibacterial drug (vancomycin hydrochloride). In order to understand the key parameters ruling the performance of this delivery system, we developed a mathematical model able to discriminate the drug diffusion inside micro-particles and within the gel phase, eventually providing to predict the drug release kinetics. The model reliability was confirmed by fitting to experimental data, proposing as a powerful theoretical approach to design and optimize such in situ delivery systems.


Subject(s)
Anti-Bacterial Agents/chemistry , Gels/chemistry , Diffusion , Drug Delivery Systems/methods , Drug Liberation/drug effects , Kinetics , Models, Theoretical , Poloxamer/chemistry , Reproducibility of Results , Vancomycin/chemistry
2.
Materials (Basel) ; 10(8)2017 Aug 21.
Article in English | MEDLINE | ID: mdl-28825682

ABSTRACT

Because of its high biocompatibility, bio-degradability, low-cost and easy availability, cellulose finds application in disparate areas of research. Here we focus our attention on the most recent and attractive potential applications of cellulose in the biomedical field. We first describe the chemical/structural composition of cellulose fibers, the cellulose sources/features and cellulose chemical modifications employed to improve its properties. We then move to the description of cellulose potential applications in biomedicine. In this field, cellulose is most considered in recent research in the form of nano-sized particle, i.e., nanofiber cellulose (NFC) or cellulose nanocrystal (CNC). NFC is obtained from cellulose via chemical and mechanical methods. CNC can be obtained from macroscopic or microscopic forms of cellulose following strong acid hydrolysis. NFC and CNC are used for several reasons including the mechanical properties, the extended surface area and the low toxicity. Here we present some potential applications of nano-sized cellulose in the fields of wound healing, bone-cartilage regeneration, dental application and different human diseases including cancer. To witness the close proximity of nano-sized cellulose to the practical biomedical use, examples of recent clinical trials are also reported. Altogether, the described examples strongly support the enormous application potential of nano-sized cellulose in the biomedical field.

3.
Expert Opin Drug Deliv ; 14(6): 797-810, 2017 06.
Article in English | MEDLINE | ID: mdl-28266887

ABSTRACT

INTRODUCTION: hepatocellular carcinoma (hcc) is the predominant form of primary liver cancer and the second leading cause of cancer-associated mortality worldwide. available therapies for hcc have limited efficacy due to often late diagnosis and the general resistance of hcc to anti-cancer agents; therefore, the development of novel therapeutics is urgently required. small-interfering rna (sirna) molecules are short, double-stranded rnas that specifically recognize and bind the mrna of a target gene to inhibit gene expression. despite the great therapeutic potential of sirnas towards many human tumors including hcc, their use is limited by suboptimal delivery. Areas covered: In this review, we outline the current data regarding the therapeutic potential of siRNAs in HCC and describe the development of effective siRNA delivery systems. We detail the key problems associated with siRNA delivery and discuss the possible solutions. Finally, we provide examples of the various siRNA delivery strategies that have been employed in animal models of HCC and in human patients enrolled in clinical trials. Expert opinion: Despite the existing difficulties in siRNA delivery for HCC, the increasing scientific attention and breakthrough studies in this field is facilitating the design of novel and efficient technical solutions that may soon find practical applications.


Subject(s)
Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , RNA, Small Interfering/administration & dosage , Animals , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/genetics , Cell Line , Humans , Liver Neoplasms/genetics
4.
Int J Pharm ; 525(2): 343-358, 2017 Jun 20.
Article in English | MEDLINE | ID: mdl-28213276

ABSTRACT

siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors' production processes and siRNAs vectors' release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors' fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.


Subject(s)
Drug Delivery Systems , RNA, Small Interfering/administration & dosage , Humans , Hydrogels/chemistry , Models, Theoretical , RNA, Small Interfering/pharmacokinetics
5.
Curr Drug Deliv ; 14(2): 158-178, 2017.
Article in English | MEDLINE | ID: mdl-27264726

ABSTRACT

Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.


Subject(s)
Biomedical Engineering , Chemical Engineering , Animals , Humans , Pharmaceutical Preparations
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