Mechanisms controlling protein release from lipidic implants: effects of PEG addition.

Department of Pharmacy, Ludwig-Maximilians-University Munich, Butenandtstrasse 5, 81377 Munich, Germany.
Journal of Controlled Release (Impact Factor: 7.26). 05/2007; 118(2):161-8. DOI: 10.1016/j.jconrel.2006.11.001
Source: PubMed

ABSTRACT Different types of tristearin-based implants for controlled rh-interferon alpha-2a (IFN-alpha) release were prepared by compression and thoroughly characterised in vitro. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was added as a co-lyophilisation agent for protein stabilisation and different amounts of polyethylene glycol (PEG) as efficient protein release modifier. To get deeper insight into the underlying mass transport mechanisms, the release of IFN-alpha, HP-beta-CD and PEG into phosphate buffer pH 7.4 was monitored simultaneously and appropriate analytical solutions of Fick's second law of diffusion were fitted to the experimental results. Importantly, the addition of only 5-20% PEG to the lipidic implants significantly altered the resulting protein release rates and the relative importance of the underlying mass transport mechanisms. The release of IFN-alpha from PEG-free implants was purely diffusion controlled. In contrast, in PEG-containing devices other phenomena were also involved in the control of protein release: the IFN-alpha release rate remained about constant over prolonged periods of time and the total amounts of mobile IFN-alpha increased. Interestingly, the release of PEG itself as well as of HP-beta-CD from the implants remained purely diffusion controlled, irrespective of the amount of added PEG. Thus, different mass transport mechanisms govern the release of the drug, co-lyophilisation agent and release modifier out of the lipidic implants.

  • [Show abstract] [Hide abstract]
    ABSTRACT: A time-domain method for characterizing the side reading of recording heads from simulated adjacent tracks is described. The method provides information such as the side-reading signal and its data-pattern dependence as well as readback-signal distortions, not obtainable from track or microtrack profiles traditionally used. The side reading of narrow-track MIG (metal-in-gap) and thin-film inductive heads produces a distinct shoulder on the readback signal, thereby increasing the noise-to-signal ratio and degrading the error-rate performance. It is observed that the side reading strongly depends on data patterns written on adjacent tracks, and certain data patterns causing large side reading can be constructed
    IEEE Transactions on Magnetics 09/1992; 28(5):2722-2724. DOI:10.1109/20.179608 · 1.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Context: The sustained release implants can be directly implanted in tumor site by surgery and are promising for cancer treatment. Objective: RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted therapy. In order to enhance tumor retention ability and long-term effect of drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co-glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials. Methods: The implants were prepared by a simple solvent evaporation method. Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of viscosity, in vitro release and drying time. Furthermore, in vivo biodistribution and antitumor activity of the implants were studied in mice with subcutaneous C6 xenografts. Results: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared by the optimized formulation was similar according to the assessment of similarity factor f2, and the release curves were fell into three phases, including a lag-period, then the second phase which was consistent with zero-order model followed by a plateau. Data of total DOX remained in implants indicated the release were faster in vivo than in vitro. Moreover, intratumoral drug amount of RGD-PPCD implants was the highest 45 days after implantation. Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity compared with PPCD and free DOX implants. Discussion and conclusion: This paper presents an exploratory research on macromolecule-drug conjugates, including RGD-PPCD and PPCD, which have the potential to be developed into long-term effect implants for tumor therapy with high efficiency and low systematic toxicity.
    Drug Delivery 03/2014; DOI:10.3109/10717544.2014.895457 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lipid excipients are attracting interest from drug developers due to their performance, ease of use, versatility and their potential to generate intellectual property through innovation in drug delivery particularly in the case of modifying drug release systems. Many articles have described the use of lipid excipients to develop matrix modified release dosage forms in a range of processing techniques, therefore a comprehensive review is timely to collect together and analyze key information. This review article focuses on the utility of lipid excipients in solid sustained drug delivery systems with emphasis on the efficiency and robustness of these systems with respect to: (i) the choice of the manufacturing process and impact on drug release, (ii) the fundamental drug release mechanisms, (iii) resistance of the drug formulation under physiological conditions and (iv) long term stability. Understanding the functionality of these versatile excipients in formulation is elementary for the development of highly robust lipid-based sustained release medicines.
    Journal of Controlled Release 06/2014; DOI:10.1016/j.jconrel.2014.06.004 · 7.26 Impact Factor