Controlled release starch-lipid implant for the therapy of severe malaria

Esfahani, Golbarg; Häusler, Olaf; Mäder, Karsten

doi:10.1016/j.ijpharm.2022.121879

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…The main dosage forms of CR-DDS include preformed implants [ 5 , 6 ], microparticles [ 7 , 8 ], and in-situ-forming implants (ISFIs) [ 9 , 10 , 11 ]. Preformed implants are made via melt extrusion, which is a continuous and well-established process in the pharmaceutical industry.…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of Novel In-Situ-Forming Oleogels

et al. 2023

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PLGA-based in situ forming implants (ISFI) often require a high amount of potentially toxic solvents such as N methyl-Pyrrolidone (NMP). The aim of the present study was to develop lipid in-situ-forming oleogels (ISFOs) as alternative delivery systems. 12-Hydroxystearic acid (12-HSA) was selected as the oleogelling agent and three different oleoformulations were investigated: (a) 12-HSA, peanut oil (PO), NMP; (b) 12-HSA, medium-chain triglycerides (MCT), ethanol; (c) 12-HSA, isopropyl myristate (IPM), ethanol. The effects of the 12-HSA concentration, preparation method, and composition on the mechanical stability were examined using a texture analysis and oscillating rheology. The texture analysis was used to obtain information on the compression strength. The amplitude sweeps were analyzed to provide information on the gel strength and the risk of brittle fractures. The frequency sweeps allowed insights into the long-term stability and risk of syneresis. The syringeability of the ISFOs was tested, along with their acute and long-term cytotoxicity in vitro. The developed ISFOs have the following advantages: (1) the avoidance of highly acidic degradation products; (2) low amounts of organic solvents required; (3) low toxicity; (4) low injection forces, even with small needle sizes. Therefore, ISFOs are promising alternatives to the existing polymer/NMP-based ISFIs.

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Section: Introductionmentioning

confidence: 99%

Development and Characterization of Novel In-Situ-Forming Oleogels

et al. 2023

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“…In our previous study, the release of Artemether (AM), with the log p-value of 3, the same as NMD, was observed over 6 days from a starch-based system. Our investigations clarified that some critical changes in the native structure of starch are needed to achieve a controlled release system . These changes are mainly formed by gelatinization of starch during the extrusion process.…”

Section: Introductionmentioning

confidence: 72%

“…Our investigations clarified that some critical changes in the native structure of starch are needed to achieve a controlled release system. 18 These changes are mainly formed by gelatinization of starch during the extrusion process. The plasticizer effect of NMD during the hot melt extrusion (HME) process has been previously reported.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Controlled Release Starch-Nimodipine Implant for Antispasmodic and Neuroprotective Therapies in the Brain

Esfahani,

Trutschel,

Reichert

et al. 2023

Mol. Pharmaceutics

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Parenteral depot systems can provide a constant release of drugs over a few days to months. Most of the parenteral depot products on the market are based on poly(lactic acid) and poly(lactide-co-glycolide) (PLGA). Studies have shown that acidic monomers of these polymers can lead to nonlinear release profiles or even drug inactivation before release. Therefore, finding alternatives for these polymers is of great importance. Our previous study showed the potential of starch as a natural and biodegradable polymer to form a controlled release system. Subarachnoid hemorrhage (SAH) is a life-threatening type of stroke and a major cause of death and disability in patients. Nimotop® (nimodipine (NMD)) is an FDA-approved drug for treating SAH-induced vasospasms. In addition, NMD has, in contrast to other Ca antagonists, unique neuroprotective effects. The oral administration of NMD is linked to variable absorption and systemic side effects. Therefore, the development of a local parenteral depot formulation is desirable. To avoid the formation of an acidic microenvironment and autocatalytic polymer degradation, we avoided PLGA as a matrix and investigated starch as an alternative. Implants with drug loads of 20 and 40% NMD were prepared by hot melt extrusion (HME) and sterilized with an electron beam. The effects of HME and electron beam on NMD and starch were evaluated with NMR, IR, and Raman spectroscopy. The release profile of NMD from the systems was assessed by high-performance liquid chromatography. Different spectroscopy methods confirmed the stability of NMD during the sterilization process. The homogeneity of the produced system was proven by Raman spectroscopy and scanning electron microscopy images. In vitro release studies demonstrated the sustained release of NMD over more than 3 months from both NMD systems. In summary, homogeneous nimodipine-starch implants were produced and characterized, which can be used for therapeutic purposes in the brain.

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“…Starch is fully biodegradable; its degradation in the body gives rise to non-toxic monomers. Starch-based materials are widely used for food packaging and as biodegradable medical products [ 21 ]. These materials exhibit excellent oxygen barrier properties, but insufficient moisture resistance and poor mechanical properties, so their use is limited.…”

Section: Introductionmentioning

confidence: 99%

Disordering of Starch Films as a Factor Influencing the Release Rate of Biologically Active Substances

et al. 2023

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The release of a spin probe (nitroxide radical) from polymer films was studied by electron paramagnetic resonance (EPR). The films were fabricated from starch having different crystal structures (A-, B-, and C-types) and disordering degrees. Film morphology (analysis of the scanning electron microscopy (SEM)) depended on the presence of dopant (nitroxide radical) to a larger extent rather than on crystal structure ordering or polymorphic modification. The presence of nitroxide radical led to additional crystal structure disordering and reduced the crystallinity index from the X-ray diffraction (XRD) data. Polymeric films made of amorphized starch powder were able to undergo recrystallization (crystal structure rearrangement), which manifested itself as an increase in crystallinity index and phase transition of the A- and C-type crystal structures to the B-type one. It was demonstrated that nitroxide radical does not form an individual phase during film preparation. According to the EPR data, local permittivity of starch-based films varied from 52.5 to 60.1 F/m, while bulk permittivity did not exceed 17 F/m, which demonstrates that local concentration of water is increased in the regions near the nitroxide radical. The mobility of the spin probe corresponds to small stochastic librations and is indicative of the strongly a mobilized state. The application of kinetic models made it possible to find out that substance release from biodegradable films consists of two stages: matrix swelling and spin probe diffusion through the matrix. Investigation of the release kinetics for nitroxide radical demonstrated that the course of this process depends on the type of crystal structure of native starch.

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Controlled release starch-lipid implant for the therapy of severe malaria

Cited by 9 publications

References 33 publications

Development and Characterization of Novel In-Situ-Forming Oleogels

Development and Characterization of Novel In-Situ-Forming Oleogels

Characterization of Controlled Release Starch-Nimodipine Implant for Antispasmodic and Neuroprotective Therapies in the Brain

Disordering of Starch Films as a Factor Influencing the Release Rate of Biologically Active Substances

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