Development and characterization of highly selective target-sensitive liposomes for the delivery of streptokinase: in vitro/in vivo studies
Authors: Manasa K Nayak
Debabrata Dash
Suresh P Vyas
Govind P Agrawal
Bhuvaneshwar Vaidya
Journal: Drug delivery (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Streptokinase; target-sensitive liposomes; targeting; thrombolytic agents; thrombus.
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, Madhya Pradesh, India and, Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract:  Streptokinase is one of the most commonly used thrombolytic agents for the treatment of thromboembolism. Short half-life of the streptokinase requires administration of higher dose which results in various side effects including systemic haemorrhage due to activation of systemic plasmin. To increase the selectivity of the streptokinase and hence to reduce side effects, various novel carriers have been developed. Among these carriers, liposomes have been emerged as versatile carrier. In the present study, highly selective target-sensitive liposomes were developed and evaluated by in vitro and in vivo studies. Prepared liposomes were found to release streptokinase in vitro following binding with activated platelets. Intravital microscopy studies in thrombosed murine model revealed higher accumulation of liposomes in the thrombus area. In vivo thrombolysis study was performed in the human clot inoculated rat model. Results of the study showed that target-sensitive liposomes dissolved 28.27 ± 1.56% thrombus as compared to 17.18 ± 1.23% of non-liposomal streptokinase. Further, it was also observed that target-sensitive liposomes reduced the clot dissolution time as compared to streptokinase solution. Studies concluded that developed liposomes might be pragmatic carriers for the treatment of thromboembolism. 

Retracted: No

PubPeer comments:
 **This paper cites a prevalence estimate which had already been declared to be in error.** ## Background: In a 2012 paper, [1] the prevalence of familial hypercholesterolemia (FH) was set at three times that of the established estimate. It was shortly thereafter declared to be in error. [2] Nonetheless, this error came back to life and now lives on in the scientific record. Part of the reason for its persistence is obfuscation: [the *original* correction was buried in a caption to a figure on page 5 of a 2013 paper]. [2] Later FH papers have been vulnerable and reveal a broader problem: **a sustained series of citation inaccuracies within FH literature have functioned as a kind of u201cerror transport system.u201d** To make my case that this problem is systemic, it is first necessary to demonstrate *that* there is a series of citation inaccuracies. To this end, I present Part 4 of Chapter 1: tracing the transportation of this particular error by way of inaccurate citations. Here are links to parts 1 through 3: - Part 1: Official 2014 Correction: https: pubpeer.com publications D69DE2E1620A86BE30004C0E458326. - Part 2: Unconventional 2013 Correction: https: pubpeer.com publications 2407D5512D3D374551C84227D66A66. - Part 3: 2016 employment of both the error and the correction as if two separate results: https: pubpeer.com publications F8B5207E775BE3943569EC6D7B765C. (Out of respect for PubPeeru2019s policy that posts be fact-based, I will wait until I present direct evidence before I announce the subject matter of Chapter 2. Sjouke et al. will play an important role.) ##Part 4: Detail of the Current Example 1.t2014 Sjouke et al. present 1 137 as a possible prevalence for familial hypercholesterolemia (FH). 2.tThe paper cites 2012 Benn et al. to support this claim. 3.tHowever, 1 137 had already been declared to be in error in 2013 Nordestgaard et al. ![file] Normally with a citation error we expect insufficient familiarity with the source. But here, several of the citing and cited authors are on both documents. We expect them to know their own work. And there are other reasons to conclude that the correction of 1 137 to 1 200 was either known or knowable: - As the above screenshots demonstrate, Nordestgaard et al. corrected Benn et al., and a citation to Nordestgaard et al. exists in Sjouke et al. Therefore, not only was the information available, but one expects that Nordestgaard et al. had been read. - These are experts. - Sjouke et al. is a study with an emphasis on prevalence. - The new prevalence of 1 137 was extreme: three times greater than the established rate. This alone is a red flag. For the reader, awareness of the problem requires extra effort, without which the correction remains camouflaged within a routine caption. As it is, the 2013 correction is as real as it remains inconsequential. References [1] tM. Benn, G. F. Watts, A. Tybjaerg-Hansen and B. G. Nordestgaard,  Familial Hypercholesterolemia in the Danish General Population: Prevalence, Coronary Artery Disease, and Cholesterol-Lowering Medication, vol. 97, no. 11, pp. 3956-3964, 2012. [2] tB. G. Nordestgaard, M. J. Chapman, S. E. Humphries, H. N. Ginsberg, L. Masana, O. S. Descamps, O. Wiklund, R. A. Hegele, F. J. Raal, J. C. Defesche, A. Wiegman, R. D. Santos, G. F. Watts, K. G. Parhofer and others,  Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society, vol. 34, no. 45, pp. 3478-3490, 2013. [3] tM. Benn, G. F. Watts, A. Tybjaerg-Hansen and B. G. Nordestgaard,  Corrigendum: Familial Hypercholesterolemia in the Danish General Population: Prevalence, Coronary Artery Disease, and Cholesterol-Lowering Medication, vol. 99, no. 12, pp. 4758-4759, 2014. ,