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Nanoparticles based on poly(propylene succinate) copolymers with poly(ethyleneglycol) (PPSu-PEG) were prepared and evaluated in vitro for their potential for a more selective delivery of cisplatin to tumors using local hyperthermia. The copolymers were synthesized through one-pot melt-polymerization under vacuum. Their thermal properties were investigated using DSC. PPSu-PEG nanoparticles loaded with cisplatin were prepared by a double emulsion method. Their colloidal stability, drug release properties, and in vitro anticancer activity were assessed. The m.p. of the synthesized PPSu-PEG copolymers ranged between 40-45 °C. The PPSu-PEG nanoparticles were stable in aqueous media with high salt concentrations. The average size of the different compositions of the PPSu- PEG nanoparticles loaded with cisplatin ranged between 77 and 126 nm and all compositions exhibited low negative ζ-potential values. The PPSU-PEG/cisplatin nanoparticles released cisplatin much faster at 42 ° C than at 37 ° C and exhibited comparable to free cisplatin cytotoxicity against HT 29 cells, which was increased when the incubation temperature was increased from 37 ° C to 42 ° C. The results justify further investigation of the potential of PPSu-PEG copolymers for the development of temperature-sensitive, targetable cisplatin nanocarriers.

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Nowadays, pharmaceutical technology and research for new drugs and formulations is of great importance, as scientists attempt to discover even more revolutionary and efficient methods to treat various diseases. At the same time the correct dosing and site targeting are equally important for clinical success. Research in sustained drug release systems is very promising towards such a direction, while it offers advantages and potential rewards contrary to traditional therapy. The drug plasma concentrations remain inside the therapeutic range for a longer time period compared to the conventional formulations. In addition, sustained release formulations may increase the likelihood for the patient to respond to the therapy, since drug formulations are generally characterized by one daily given dose. The rate at which a drug is released from a sustained-release formulation depends upon many factors, while excipients play the most important role. Most sustained release formulations are based on biodegradable polymers in the form of a drug-encapsulating matrix or membrane. Examples range from monolithic devices, polymer-coated capsules and implant devices, hydrogels, to injectable systems based on suspensions of micro-, nanospheres or polymer solutions [1-5]. The advantages and disadvantages of these different formulation systems are being extensively discussed in the present review.