| In the medicine of the clinical usage, there have a group ofmedicine which need the long-term (a few month even few year)stability to administer, for example anti-cancer medicine, quit thepoison thing, cardiovascular medicine, avoid pregnancy the medicineand vaccine etc. To this group of medicine, it exists many problemsto solve when we adopt the common drug delivery system: thepatient needs take medicine frequently or accept to be injectedperhaps, breaking off taking the drug will result in the relapsing ofthe illness, it will bring a world of inconvenience to the patient;besubjected to the influences, such as stomach and intestinesenvironment and the" first pass effect"of the liver etc., the biologicalavailability of the drug is low, the individual difference is big;it can'tkeep the stable blood drug level with a long time, it cuts down thetreatment result of the drug and buildups side effect. The implanation controlled release drug delivery system(ICRDDS) is a group of control release praeparatum that implantinto the body or hypo. by surgical operation or inject into hypo.through transfixion pin. The ICRDDS has the followingadvantage:(1) it can eliminate the hump or valley phenomenoncreated by taking the drug periodically and dosage's asymmetry andreleas the drug with a permanent velocity at specified function locusand retain curative concentration and chalk the curative effect with asmaller dosage of the drug;(2) it can avoid the side effects to theother organizations in vivo when the drug effects at the target site;(3)it can avoid the quick metabolism of some medicine and prolongtheir half-life in vivo;(4) it can dosage by the implantation pathwaywhen it's hard to dosage by other paths;(5) it can avoid the unwellfeeling, hurt , pain and sufferings etc for cause, and can take outquickly once the severe allergic response or the side effect takingplace. ICRDDS is a biodegradable high molecular polymer, afterbeing implanted in vivo it will be biodegradabled with the releasingof the the drug, and doesn't need another surgical operation to take itout, so we can raise the curative effect, control the releasing velocity,reduce the poisonous side effect and reduce the dosage frequency etc,it can be easily accepted by the patients.Because of its favourable anti-cancer activity and specialmechanism of action in various tumor models, the paclitaxel get theextensive application in many cancer such as ovarian cancer,metastatic breast cancer and nonsmall-cell lung cancer etc. Thepaclitaxel itself is dissolve in the water scarcely, which limit theclinical application of it, if we can produce a kind of newpraeparatum by the paclitaxel, we can not only solve the difficulty inthe application of oil, but also raise the biological availability of thedrug, thus can reduce the dosage.Our experiments are topics assistanced by national naturalscience foundation of china (the item serial number 50373043), wechoosed biodegradabled PLLA-PEG750 with favourablebiocompatibility to be the carrying agent, and prepared fibers whichcontained 2.5wt% the paclitaxel by electrospinning technology toimplant the new dosage form to research, and proved thepaclitaxel-PLLA-PEG750 fibers' safety and efficacy in themanagement of ovarian cancer by chemotherapy. The expected newimplantation controlled released dosage form to the anti-tumormedicine, finally will be applied in clinical treatment of the tumors,such as ovarian cancer and hepatoma etc successfully.This research express that PLLA-PEG750 is safety, have nocytotoxicity, the 2.5% paclitaxel-PLLA-PEG750 fibers haveobviously controlled released effectiveness, whose drug releasing iscorrespond the requirement of the zero order kinetics, it can affect atSKOV3 cell in vitro, repress the generation of the tumor cellseffectively, increase G2/M period percentage, interrupt the cell cycleproceeding, and achieve the motive to inhibit the tumor cells' growththrough cell apoptosis and cell necrosis. The implanation controlledrelease drug delivery through fibers reduced the dosage frequency,reduced the poisonous side effect of intravenous injection, improvedthe weakness of the paclitaxe that dissolve in the water scarcely,increased effective utilization of the paclitaxe, the 2.5% paclitaxe-PLLA -PEG750 fibers' inhibition ratio to the ovarian cancer cells hasachieved or approached the group with single paclitaxe.The current drugs control releasing dosage form essentiallyexist some problems such as low drug loaded, the drugs releaseingsuddenly etc., this is also the problem that all the people who arerecearching drug controlled releasing expect to resolve. We can say,these two problems is a bottleneck of the drug controlled releasing 'stechnique development. The aliphatic series polyester biodegradablehigh molecular polymer, drug controlled releasing andelectrospinning technology are the most popular fields ofinternational research at present, they are reciprocal chiasma at thesame time. Utilizing electrospinning technology, at the time whenmaking the aliphatic series polyester into electrospinning fibers,implementing the drug loaded, we can combine the three organically,hope to resolve the above-mentioned two problems.The PLLA-PEG750 is a kind of control releasing vector ideally,the implanation controlled releasing drug delivery system of theelectrospinning fibers have above-mentioned special superiority,particularly is larger valuable to the anti-tumor drugs which areapplied extensively in clinical. Our initial research has alreadyconfirmed the in-service use value and the feasibility of theimplanation controlled releasing drug delivery system of theelectrospinning fibers, and its achievement will still have theextensive adaptability, it can be used to the alteration of many drugsdosage form and satisfy the request of the drug controlled releasing,and have a vast foreground for development and application. |
PDF Full Text Request