Characterization of Ion-Exchange Fibers for Controlled Drug Delivery

Increasing attention has been focused on methods that deliver pharmacologically active compounds (e.g. drugs, peptides and proteins) in a controlled fashion, so that constant, sustained, site-specific or pulsatile action can be attained. Ion-exchange resins have been widely studied in medical and pharmaceutical applications, including controlled drug delivery, leading to commercialisation of some resin based formulations. Ion-exchangers provide an efficient means to adjust and control drug delivery, as the electrostatic interactions enable precise control of the ion-exchange process and, thus, a more uniform and accurate control of drug release compared to systems that are based only on physical interactions. Unlike the resins, only few studies have been reported on ion-exchange fibers in drug delivery. However, the ion-exchange fibers have many advantageous properties compared to the conventional ion-exchange resins, such as more efficient compound loading into and release from the ion-exchanger, easier incorporation of drug-sized compounds, enhanced control of the ion-exchange process, better mechanical, chemical and thermal stability, and good formulation properties, which make the fibers attractive materials for controlled drug delivery systems. In this study, the factors affecting the nature and strength of the binding/loading of drug-sized model compounds into the ion-exchange fibers was evaluated comprehensively and, moreover, the controllability of subsequent drug release/delivery from the fibers was assessed by modifying the conditions of external solutions. Also the feasibility of ion-exchange fibers for simultaneous delivery of two drugs in combination was studied by dual loading. Donnan theory and theoretical modelling were applied to gain mechanistic understanding on these factors. The experimental results imply that incorporation of model compounds into the ion-exchange fibers was attained mainly as a result of ionic bonding, with additional contribution of non-specific interactions. Increasing the ion-exchange capacity of the fiber or decreasing the valence of loaded compounds increased the molar loading, while more efficient release of the compounds was observed consistently at conditions where the valence or concentration of the extracting counter-ion was increased. Donnan theory was capable of fully interpreting the ion-exchange equilibria and the theoretical modelling supported precisely the experimental observations. The physico-chemical characteristics (lipophilicity, hydrogen bonding ability) of the model compounds and the framework of the fibrous ion-exchanger influenced the affinity of the drugs towards the fibers and may, thus, affect both drug loading and release. It was concluded that precisely controlled drug delivery may be tailored for each compound, in particularly, by choosing a suitable ion-exchange fiber and optimizing the delivery system to take into account the external conditions, also when delivering two drugs simultaneously.

Musculoskeletal disorders and psychosocial factors at work : Effects of a participatory ergonomics intervention in a cluster randomized controlled trial

This study examined the efficacy of a participatory ergonomics intervention in preventing musculoskeletal disorders (MSDs) and changing unsatisfactory psychosocial working conditions among municipal kitchen workers. The occurrence of multiple-site musculoskeletal pain (MSP) and associations between MSP and psychosocial factors at work over time were studied secondarily. A cluster randomized controlled trial was conducted during 2002-2005 in 119 municipal kitchens with 504 workers. The kitchens were randomized to an intervention (n = 59) and control (n = 60) group. The intervention lasted 11 to 14 months. The workers identified strenuous work tasks and sought solutions for decreasing physical and mental workload. The main outcomes were the occurrence of and trouble caused by musculoskeletal pain in seven anatomical sites, local musculoskeletal fatigue after work, and musculoskeletal sick leaves. Psychosocial factors at work (job control, skill discretion, co-worker relationships, supervisor support, mental strenuousness of work, hurry, job satisfaction) and mental stress were studied as intermediate outcomes of the intervention. Questionnaire data were collected at three months intervals during the intervention and the one-year post-intervention follow-up. Response rates varied between 92 % and 99 %. In total, 402 ergonomic changes were implemented. In the control group, 80 changes were spontaneously implemented within normal activity. The intervention did not reduce perceived physical workload and no systematic differences in any health outcomes were found between the intervention and control groups during the intervention or during the one-year follow-up. The results suggest that the intervention as studied in the present trial was not more effective in reducing perceived physical workload or preventing MSDs compared with no such intervention. Little previous evidence of the effectiveness of ergonomics interventions in preventing MSDs exists. The effects on psychosocial factors at work were adverse, especially in the two of the participating cities where re-organization of foodservices timed simultaneously with the intervention. If organizational reforms at workplace are expected to occur, the execution of other workplace interventions at the same time should be avoided. The co-occurrence of musculoskeletal pain at several sites is observed to be more common than pain at single anatomical sites. However, the risk factors of MSP are largely unknown. This study showed that at baseline, 73 % of the women reported pain in at least two, 36 % in four or more, and 10 % in six to seven sites. The seven pain symptoms occurred in over 80 different combinations. When co-occurrence of pain was studied in three larger anatomical areas (neck/low back, upper limbs, lower limbs), concurrent pain in all three areas was the most common combination (36 %). The 3-month prevalence of MSP (≥ 3 of seven sites) varied between 50 % and 61 % during the two-year follow-up period. Psychosocial factors at work and mental stress were strong predictors for MSP over time and, vice versa, MSP predicted psychosocial factors at work and mental stress. The reciprocality of the relationships implies either two mutually dependent processes in time, or some shared common underlying factor(s).

Organized Nanostructures of Thermoresponsive Poly(N-isopropylacrylamide) Block Copolymers Obtained Through Controlled RAFT Polymerization

Kontrolloidut radikaalipolymerointimenetelmät, kuten RAFT-polymerointi, ovat moderni tapa valmistaa polymeerejä säädellysti. RAFT-polymeroinnilla polymeerien ketjunpituutta, moolimassajakaumaa, mikrorakennetta (taktisuus, järjestys), koostumusta ja funktionaalisuutta kyetään hallitsemaan. Siten menetelmällä voidaan valmistaa uudenlaisia polymeeriarkkitektuureja, kuten blokki- ja tähtipolymeerejä, sekä hybridimateriaaleja ja biokonjugaatteja. Polymeeristen rakennuspalikoiden itsejärjestyminen, missä huolellisesti syntetisoidut polymeerit järjestyvät halutulla tavalla nanoskaalassa, on suosittu tutkimuskohde materiaalitieteessä. On huomattava, että blokkipolymeerien itsejärjestyminen on vielä suhteellisen nuori tutkimusaihe. Tämän hetkiset polymeeriset nanomateriaalit ovat suhteellisen yksinkertaisia luonnon luomuksiin verrattuina, tarjoten jatkuvasti uusia mahdollisuuksia seuraavan sukupolven polymeereille. Tässä työssä RAFT-polymeroinnilla syntetisoitiin amfifiilisiä di- ja triblokkikopolymeerejä sekä tutkittiin niiden järjestymistä nanorakenteiksi. Kaikissa blokkikopolymeereissä käytettiin lämpöherkkää poly(N-isopropyyliakryyliamidia). Siten polymeerit ja tutkitut materiaalit reagoivat lämpötilanmuutokseen ympäristössä eli ovat ns. ympäristöherkkiä. Työssä tutkittiin taktisuuden kontrollointia N-isopropyyliakryyliamidin RAFT-polymeroinnissa. Polymeerin taktisuutta sekä ketjunpituutta ja blokkijärjestystä säätämällä voitiin hallita polymeerin itsejärjestymistä vesiliuoksessa. Amfifiiliset polymeerit järjestyivät laimeissa vesiliuoksissa erilaisiksi misellirakenteiksi, muodostaen ns. mikrosäiliöitä. Tällaisilla polymeereillä odotetaan olevan sovelluksia esim. lääkeainevapautuksessa. Amfifiilejä käytetään myös esimerkiksi apuaineina pinnoitteissa ja kosmetiikassa. Kiinteässä tilassa tutkitut triblokkikopolymeerit muodostivat teoreettisesti ennustettuja morfologioita. Lämpöherkän materiaalin hydrogeelit toimivat suodatinmembraanina nanokokoluokassa. RAFT-polymeroinnilla syntetisoituja polymeereja voidaan sellaisenaan käyttää kultananopartikkeleiden päällystämiseen. Kultananopartikkelit ovat erittäin kiinostavia mm. niiden stabiilisuuden ja ainutlaatuisten pintaominaisuuksien vuoksi. Kun amfifiilisiä polymeerejä kiinnitettiin kultapartikkelin pinnalle, sen liuos- ja optisia ominaisuuksia voitiin säädellä pH:n ja lämpötilan avulla. Tällaisilla kultananopartikkeleilla on sovelluksia mm. diagnostiikassa, sensoreina ja solukuvauksessa.