Studies on the lipase induced degradation of lipid based drug delivery systems

Implants as Sustained Release Delivery Devices for Vaccine Antigens

“…In the pharmaceutical context, twin-screw extrusion has been used successfully for the preparation of implants from triglycerides and mixtures of triglycerides for the delivery of drugs and proteins (Reitz and Kleinebudde 2007 ;Schulze and Winter 2009 ;Sax et al 2012a ). Twin-screw extrudates have been prepared containing IFN-α-2a Sax et al 2012a ) and lysozyme (Schwab et al 2009 ;Sax and Winter 2012 ). However, this method has not been utilized for the preparation of implants for vaccine delivery where the implants have a much lower protein/peptide load (5 mg in drug delivery vs. 1-50 μg for vaccines).…”

“…Biodegradable systems may degrade via bioerosion processes, meaning that over the time of incubation (or implantation), the diffusional barrier of the matrix becomes smaller. If, for example, the antigen is incorporated into a lipid matrix, this matrix may undergo enzymatic degradation via the action of lipases, as shown by Schwab et al (2009Schwab et al ( , 2009Schwab et al ( , 2013. The occurrence and impact of lipase degradation depends on the type of lipid.…”

“…This results in the observation of a decrease in drug release; a constant drug release profi le can therefore not be achieved using these systems. Also, the time required for biodegradation depends heavily on the choice of lipid and the manufacturing technique (Schwab et al 2009 ;Sax et al 2012b ). Sax et al for example, observed that surprisingly, implants prepared by twin screw extrusion from a mixture of a high melting lipid (D118), a low melting lipid (H12 or E85), and a pore-forming agent (PEG 6000) showed biodegradability when tested in vivo in a rabbit model for over 6 months (Sax et al 2012b ).…”

Mechanistic studies on the release of lysozyme from twin-screw extruded lipid implants

“…Over the last 10 years lipids gained more interest as delivery platform for therapeutic proteins [4,[6][7][8][9] as they do not show the shortcomings of the commonly used PLA and PLGA polymers, which produce reactive degradation products during erosion [10][11][12]. Lipid implants were shown to be biocompatible [13,14] and biodegradable [14,15] and maintained the stability of lyophilized protein drugs like recombinant human interferon-α2a during production, storage and in-vitro release [16,17]. Release from lipid based implant systems has been shown to be mainly driven by water entry into the (porous) matrix systems and diffusion of protein in water-filled pores of the implants [18,19].…”

Release pathways of interferon α2a molecules from lipid twin screw extrudates revealed by single molecule fluorescence microscopy

“…During the last decade, lipids gained more and more interest as matrix materials for the preparation of parenterally applicable formulations [7][8][9][10][11] as they show good biocompatibility [12,13] and biodegradability [12,14]. Sustained release of macromolecules from various lipidic devices was proven for protein drugs including brain-derived neurotrophic factor (BDNF) [17], recombinant human interferon α2a (IFNα) [7,[15][16][17], insulin [7], interleukin-18 [9], BSA [18] and vaccines [19].…”