Special Issue "Macromolecules Applied to Pharmaceutics"

Guest Editor
Prof. Dr. Tommasina Coviello
Faculty of Pharmacy, Department of Drug Chemistry and Technologies, "Sapienza" University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Website: http://ctf.frm.uniroma1.it/cgi-bin/campusnet/docenti.pl/Show?_id=coviello
E-mail:

Summary

This special issue, “Macromolecules applied to Pharmaceutics” is devoted to a peculiar branch of polymer science that is rapidly growing in the last decades.
It is of interest, therefore, to publish both reviews and original research papers to illustrate the general trend in current research.
Polymers can act, in different ways, as carriers for drug delivery and as peculiar therapeutic agents to be delivered. In the past few decades macromolecules have evolved from off-the-shelf materials originally developed for applications unrelated to biomedicine to materials specifically designed for particular applications and exhibiting intended biomedical functions. The design of new polymeric devices requires the combination of knowledge among scientist from different fields such biology, medicine, pharmaceutical sciences, chemistry, physics and materials science.
In that sense I wish to thank all the authors for their cooperation and support in the preparation of the present issue.

Submission

All papers should be submitted to molecules@mdpi.org with copy to the guest editor. To be published continuously until the deadline and papers will be listed together at the special websites.

Submitted papers should not have been previously published nor be currently under consideration for publication elsewhere. All papers are refereed through a peer review process. A guide for authors, sample copies and other relevant information for submitting papers are available on the Instructions for Authors page. Molecules is an international peer-reviewed monthly journal published by Molecular Diversity Preservation International.

Please visit the Instructions for Authors page before submitting a paper. Open Access publication fees are 800 CHF per paper. English correction fees (250 CHF) will be added in certain cases (1050 CHF per paper for those papers that require extensive additional formatting and/or English corrections.).

Synthetic and natural polymers for drug/gene delivery and/or medical devices; New aspects of macromolecule uses in the dosage form design; Characterization of polymers used in the pharmaceutics field; Biomaterials; Macromolecular pro-drugs; Delivery of macromolecular drugs; Hydrogel delivery systems; Micro- and Nano-technological approaches for the delivery of macromolecules; Pharmaceutical applications of dendrimers; Polymeric nanocarriers for drug delivery; Polymer-drug conjugates for drug targeting; Stimuli-responsive polymeric systems for biomedical applications; Polymeric scaffolds for tissue engineering.

Manuscript ID: molecules-macropharm-20090212-us-Raucher
Type of Paper: Article
Title: Application of Thermally Responsive Elastin-like Polypeptide Fused to a Lactoferrin-derived Peptide for Treatment of Pancreatic Cancer
Authors: Iqbal Massodi, Emily Thomas and Drazen Raucher *
Affiliation: Department of Biochemistry, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA
* Author to whom correspondence should be addressed; E-mail: draucher@biochem.umsmed.edu.
Abstract: A well characterized, peptide derivative of bovine lactoferrin, L12, has been shown to possess anticancer properties in multiple cell lines. However, adverse side effects in normal tissues and poor plasma kinetics that hinder the clinical effectiveness of current chemotherapeutics also deter the potential for effective delivery of this N-terminus derived L12 peptide. To overcome these limitations, we have developed a polypeptide carrier, elastin-like polypeptide (ELP), that has the potential to thermally target therapeutic peptides and chemotherapeutics to the tumor site. We conjugated the L12 peptide to our thermally responsive ELP carrier. The coding sequence of ELP-L12 was further modified with a membrane transduction domain derived from the HIV-1 Tat protein. The thermally responsive Tat-ELP1-L12 is soluble in aqueous solutions at 37°C but aggregates near 41°C, which makes Tat-ELP1-L12 ideal for targeting to solid tumors on application of focused hyperthermia. We observed that under hyperthermia conditions at 42°C, Tat-ELP1-L12 mediated cytotoxicity in Mia-Paca-2 pancreatic adenocarcinoma cells was enhanced by nearly thirty-fold. We investigated the mechanisms of cell death and found evidence of mitochondrial membrane depolarization and caspase activation, which is characteristic of apoptosis, as well as, increased membrane permeability, as shown by LDH release. These results suggest that Tat-ELP1-L12 possesses cytotoxic properties to cancer cells in vitro and may have the potential to provide an effective vehicle to thermally target solid tumors.
Keywords: Elastin-like polypeptide; L12; Hyperthermia; Thermal targeting; Drug delivery; Pancreatic cancer

Manuscript ID: molecules-macropharm-20090219-gr-Bikiaris
Type of Paper: Article
Title: Novel Biodegradable Aliphatic Polyesters: Synthesis and Application as Drug Carriers for Nanoencapsulation of Raloxifene HCl
Authors: Dimitrios Bikiaris ^1,*, Vassilios Karavelidis ¹ and Evangelos Karavas ²
Affiliations: ¹ Laboratory of Organic Chemical Technology, Chemistry Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece
² Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str 6, Pallini Attikis, 153 51 Attiki, Greece
Abstract: Raloxifene HCl is a drug with poor bioavailability due to very low water solubility. The results of several large clinical trials have shown that raloxifene reduces the rate of bone loss at both distal sites and in the spinal column and may increase bone mass at certain sites. The aim of the present study is to use biodegradable and biocompatible aliphatic polyesters in the form of nanoparticles in order to encapsulate the Raloxifene HCl. For this reason a series of novel biodegradable poly(ethylene succinate-co-propylene adipate) (PESu-co-PPAd) copolymers were synthesized following the polycondensation method. Poly(propylene succinate) (PPSu) and poly(propylene adipate) (PPAd) were also used for comparison.. The polyesters were characterized by intrinsic viscosity measurements, enzymatic hydrolysis measurements, Nuclear Magnetic Resonance Spectroscopy (¹Η-NMR and ¹³C-NMR), Wide-angle X-Ray Diffractometry (WAXD) and Thermogravimetric Analysis (TGA). The nanoparticles containing the drug were prepared by a modification of the co-precipitation method and were studied by WAXD, Fourier Transformation Infrared Spectroscopy (FT-IR), dynamic light scattering (DLS) for size distribution determination, Scanning Electron Microscopy (SEM) and drug dissolution testing. The interactions between the polymers and the drug seem to be limited. The drug occurs in crystalline form in the nanoparticles and the nanoparticles size was in the range of 150-350 nm, depending on the used polymer. The drug dissolution study indicated an initial sustained release stage, followed by very slow rates.
Keywords: raloxifene HCl; poly(propylene succinate); poly(propylene adipate); block copolymers; biodegradable aliphatic polyesters; nanoparticles

Manuscript ID: molecules-macropharm-20090220-tr-Ozsoy
Type of Paper: Review
Title: Drugs with High Molecular Weight Applied via Nasal Route
Authors: Yıldız Ozsoy * and Erdal Cevher
Affiliation: Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 34116-Universite, Istanbul, Turkey
* Author to whom correspondence should be addressed: Address: as above; Tel.: + 90 212 440 02 72; Fax: + 90 212 440 02 52; E-mail: yozsoy@istanbul.edu.tr.
Abstract: The nasal drug delivery may be used for either local or systemic effects. Drugs with low molecular weight are rapidly absorbed through nasal mucosa. The main rationales for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of nasal epithelium. Despite the many advantages of the nasal route, some limitations such as high molecular weight (HMW) of drugs impede the drug absorption through nasal mucosa. Recent studies have particularly focused on the nasal application of HMW therapeutic agents such as peptite-protein drugs and vaccines intended for systemic effect. Due to their hydrophilic structure, nasal bioavailability of protein and peptide drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are cleared rapidly from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption.
In this review article, nasal route and transport routes across nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nano- and micro-particular carrier systems will be summarised.
Keywords: Macromolecular drugs, nasal delivery, vaccine

Manuscript ID: molecules-macropharm-20090423-es- Veiga
Title: Characterization and Dissolution Study of Chitosan Freeze-dried Systems for Drug Controlled Release
Author: R. Ruiz-Caro¹, M. D. Veiga^1,2
Affiliation: ¹Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Spain
²Unidad de Biotransformaciones Industriales, Parque Científico de Madrid, Tres Cantos, Madrid, Spain
Corresponding author: M.D. Veiga. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040-Madrid, Spain; Tel. +34913941741; Fax: +34913941736; e-mail: mdveiga@farm.ucm.es
Abstract: Freeze-dried systems (L) comprising chitosan (CS) and Caffeine (CAF), for oral administration, have been developed. Different proportions of CS and CAF have been used in the preparation of freeze-dried systems. Differential scanning calorimetry, hot stage microscopy and X-ray diffraction powder have been used in order to characterize the systems prepared. X- ray diffraction patterns showed that there were not interactions between CAF and CS molecules within the freeze-dried systems and the crystallinity of CAF was decreased. Swelling and dissolution tests were carried out in two different media (demineralized water and pH progressive medium) in order to know their influence over CAF/CS systems behaviour. Characteristic swelling behaviour of freeze-dried CS systems (imbibition and dissolution processes) was influenced by CS and CAF proportions within the formulations, and by the nature of the medium due to CS solubility pH dependent. Release of CAF from lyophilized systems was conditioned by swelling process and it should be possible to obtain a CAF/CS binary system with a specific time for total drug release including concrete proportions of both components. Furthermore, freeze-drying process allowed to obtain feasible systems for controlled release of CAF until the total amount of drug was released.
Keywords: Caffeine; Chitosan; freeze-dried systems; swelling and behaviour; controlled releas