Effect of sterical stabilization on macrophage uptake in vitro and on thickness of the fixed aqueous layer of liposomes made from alkylphosphocholines

Zeisig, Reiner; Shimada, Kazuhiko; Hirota, Shun; Arndt, Dieter

doi:10.1016/s0005-2736(96)00167-8

Cited by 98 publications

(40 citation statements)

References 31 publications

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“…PDI is the ratio of standard deviation to mean droplet size (Centis & Vermette, 2008). A small value of PDI reveals a homogenous monodisperse size distribution, while a large PDI value reflects a higher heterogeneous poly-disperse size distribution (Zeisig et al, 1996;Basha et al, 2013). Figure 1.…”

Section: Effect Of Formulation Variables On the Particle Size And Pdimentioning

confidence: 99%

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

et al. 2016

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Migraine attack is a troublesome physiological condition associated with throbbing, intense headache, in one half of the head. Zolmitriptan is a potent second-generation triptan, prescribed for patients with migraine attacks, with or without an aura, and cluster headaches. The absolute bioavailability of zolmitriptan is about 40% for oral administration; due to hepatic first metabolism. Nasal administration would circumvent the pre-systemic metabolism thus increasing the bioavailability of zolmitriptan. In addition, due to the presence of microvilli and high vasculature, the absorption is expected to be faster compared to oral route. However, the bioavailability of nasal administered drugs is particularly restricted by poor membrane penetration. Thus, the aim of this work is to explore the potential of novel nanovesicular fatty acid enriched structures (novasomes) for effective and enhanced nasal delivery of zolmitriptan and investigate their nose to brain targeting potential. Novasomes were prepared using nonionic surfactant, cholesterol in addition to a free fatty acid. A 2 3 full factorial design was adopted to study the influence of the type of surfactant, type of free fatty acid and ratio between the free fatty acid and the surfactant on novasomes properties. The particle size, entrapment efficiency, polydispersity index, zeta potential and % zolmitriptan released after 2 h were selected as dependent variables. Novasomes were further optimized using Design Expert Õ software (version 7; Stat-Ease Inc., Minneapolis, MN), and an optimized formulation composed of Span Õ 80:Cholesterol:stearic acid (in the ratio 1:1:1) was selected. This formulation showed zolmitriptan entrapment of 92.94%, particle size of 149.9 nm, zeta potential of À55.57 mV, and released 48.43% zolmitriptan after 2 h. The optimized formulation was further examined using transmission electron microscope, which revealed non-aggregating multi-lamellar nanovesicles with narrow size distribution. DSC, XRD examination of the optimized formulation confirmed that the drug have been homogeneously dispersed throughout the novasomes in an amorphous state. In-vivo bio-distribution studies of 99m Tc radio-labeled intranasal zolmitriptan loaded novasomes were done on mice, the pharmacokinetic parameters were compared with those following administration of intravenous 99m Tc-zolmitriptan solution. Results revealed the great enhancement in zolmitriptan targeting to the brain, with drug targeting potential of about 99% following intranasal administration of novasomes compared with the intravenous drug solution. Zolmitriptan loaded novasomes administered via the nasal route may therefore constitute an advance in the management of acute migraine attacks.

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Section: Effect Of Formulation Variables On the Particle Size And Pdimentioning

confidence: 99%

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

et al. 2016

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“…Grafting liposomes with polyethylene glycol (PEG) has been shown to prolong liposome circulation in vivo (26)(27)(28). The presence of PEG attracts water to the liposome surface and provides a barrier against opsonins and cells of the RES (29). In addition, PEG neutralizes the surface charge of liposomes, decreasing the interaction between charged phospholipid head groups and opsonizing proteins (26).…”

Section: Introductionmentioning

confidence: 99%

PEGylation of a Factor VIII–Phosphatidylinositol Complex: Pharmacokinetics and Immunogenicity in Hemophilia A Mice

Peng

Kosloski

Nakamura

et al. 2011

AAPS J

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Abstract. Hemophilia A is an X-linked bleeding disorder caused by the deficiency of factor VIII (FVIII). Exogenous FVIII is administered therapeutically, and due to a short half-life, frequent infusions are often required. Fifteen to thirty-five percent of severe hemophilia A patients develop inhibitory antibodies toward FVIII that complicate clinical management of the disease. Previously, we used phosphatidylinositol (PI) containing lipidic nanoparticles to improve the therapeutic efficacy of recombinant FVIII by reducing immunogenicity and prolonging the circulating half-life. The objective of this study is to investigate further improvements in the FVIII-PI formulation resulting from the addition of polyethylene glycol (PEG) to the particle. PEGylation was achieved by passive transfer of PEG conjugated lipid into the FVIII-PI complex. PEGylated FVIII-PI (FVIII-PI/PEG) was generated with high association efficiency. Reduced activity in vitro and improved retention of activity in the presence of antibodies suggested strong shielding of FVIII by the particle; thus, in vivo studies were conducted in hemophilia A mice. Following intravenous administration, the apparent terminal half-life was improved versus both free FVIII and FVIII-PI, but exposure determined by area under the curve was reduced. The formation of inhibitory antibodies after subcutaneous immunization with FVIII-PI/PEG was lower than free FVIII but resulted in a significant increase in inhibitors following intravenous administration. Passive transfer of PEG onto the FVIII-PI complex does not provide any therapeutic benefit.

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“…[3][4][5] The fixed aqueous layer thickness (FALT) around the liposome was measured using interfacial electrochemistry and it was reported that the FALT of PEG-modified liposomes increased in comparison with PEG unmodified liposomes. 6,7) PEGalkyl lipid derivatives have different physicochemical properties depending on the molecular weight of the PEG-moiety, the fatty acid length as the anchor, and the conformation of the spacer unit. In our previous paper, we reported the mixed PEG-modified liposomes obtained with a mixture of PEG of short and long polyoxyethylene chains were useful.…”

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confidence: 99%

Characterization of Novel Mixed Polyethyleneglycol Modified Liposomes

Sugiyama

Sadzuka

2007

Biological & Pharmaceutical Bulletin

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In our previous paper, mixed polyetheleneglycol (PEG) modification of liposomes by a mixture of 1-monomethoxypolyethyleneglycol-2,3-distearoylglycerol (PEG-DSG) with short polyoxyethylene chain and PEG-DSG with long one was shown to increase fixed aqueous layer thickness (FALT) around the liposomal membrane, and this was useful in vivo. In this study, we investigated the characterization of mixed PEG modification of liposomes with different anchors (PEG2000-DSG and PEG2000-cholesterol (CHO)). When the liposomes was modified by a mixture of PEG2000-DSG and PEG2000-CHO, FALT was increased compared to that of each single PEG-lipids modification and the most suitable mix modification (PEG2000-DSG : PEG2000-CHO‫3؍‬ : 1) showed a maximum FALT. This phenomenon was speculated to be based on the difference in the insertion state of the PEG anchor unit in the liposomal membrane. PEG-CHO-modified liposomes (single or mixed PEG-modified liposomes) were easily incorporated into the liposomal membranes compared with that of single PEG-DSG-modified liposomes. Namely, it was considered that the cholesterol anchor as a single chain was able to be easily introduced, compared with the DSG anchor as two chains, and induced some interaction with both PEG modification. In conclusion, it is expected that novel PEG-modified liposomes with PEG2000-DSG and PEG2000-CHO (3 : 1) had superior physicochemical properties.

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Effect of sterical stabilization on macrophage uptake in vitro and on thickness of the fixed aqueous layer of liposomes made from alkylphosphocholines

Cited by 98 publications

References 31 publications

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

PEGylation of a Factor VIII–Phosphatidylinositol Complex: Pharmacokinetics and Immunogenicity in Hemophilia A Mice

Characterization of Novel Mixed Polyethyleneglycol Modified Liposomes

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