Intracarotid Delivery of Drugs

Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

doi:10.1097/aln.0b013e318182c81b

Cited by 56 publications

(30 citation statements)

References 156 publications

(163 reference statements)

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“…4, 28-30 However, despite intensive efforts, IA drug delivery has yet to make a significant therapeutic impact in the treatment of brain cancers—a failure it shares with many other malignant brain tumor treatments. This is somewhat remarkable given that for cancers of other organs such as liver, breast, eye, and even extra-cranial tumors of the head and neck, IA chemotherapy is fairly effective.…”

Section: Discussionmentioning

confidence: 99%

“…In general, IA drugs are most effective in three specific situations: 1. when there is low regional blood flow, 2. when there is high regional drug extraction, and 3. when the drug is rapidly cleared from the systemic circulation. 30 In addition, more consistent tissue drug concentrations are achieved by pulsed or bolus dosing. 30, 35, 36 Therefore, our approach to IA delivery to the brain uses transient blood flow reduction with concurrent intracarotid bolus injection.…”

Section: Discussionmentioning

confidence: 99%

“…30 In addition, more consistent tissue drug concentrations are achieved by pulsed or bolus dosing. 30, 35, 36 Therefore, our approach to IA delivery to the brain uses transient blood flow reduction with concurrent intracarotid bolus injection. 10-12 IA injection during transient cerebral hypoperfusion generates high cerebral arterial drug concentrations, increases drug transit time through brain tissue, and minimizes drug binding to blood proteins and cell components.…”

Section: Discussionmentioning

confidence: 99%

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Cerebral Hypoperfusion-Assisted Intra-arterial Deposition of Liposomes in Normal and Glioma-Bearing Rats

Joshi¹,

Singh‐Moon²,

Ellis³

et al. 2015

Neurosurgery

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Background Optimizing liposomal vehicles for targeted delivery to the brain has important implications for the treatment of brain tumors. The promise of efficient, brain-specific delivery of chemotherapeutic compounds via liposomal vehicles has yet to be achieved in clinical practice. Intra-arterial injection of specially designed liposomes may facilitate efficient delivery to the brain and to gliomas. Objective To test the hypothesis that cationic liposomes may be effectively delivered to both normal and glioma-bearing brain tissue utilizing a strategy of intra-arterial injection during transient cerebral hypoperfusion. Methods Cationic, anionic, and neutral liposomes were separately injected via the internal carotid artery of healthy rats during transient cerebral hypoperfusion. Rats bearing C6 gliomas were similarly injected with cationic liposomes. Liposomes were loaded with DilC18(5) dye whose concentrations can be measured by light absorbance and fluorescence methods. Results After intra-arterial injection, a robust uptake of cationic as compared to anionic and neutral liposomes into brain parenchyma was observed by diffuse reflectance spectroscopy. Post mortem multispectral fluorescence imaging revealed that liposomal cationic charge was associated with more efficient delivery to the brain. Cationic liposomes were also readily observed within glioma tissue after intra-arterial injection. However, over time, cationic liposomes were retained longer and at higher concentrations in the surrounding, peri-tumoral brain than in the tumor core. Conclusion This study demonstrates the feasibility of cationic liposome delivery to brain and glioma tissue after intra-arterial injection. Highly cationic liposomes directly delivered to the brain via an intracarotid route may represent an effective method for delivering anti-glioma agents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cerebral Hypoperfusion-Assisted Intra-arterial Deposition of Liposomes in Normal and Glioma-Bearing Rats

Joshi¹,

Singh‐Moon²,

Ellis³

et al. 2015

Neurosurgery

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“…Although an attractive idea, IA drug delivery has not found widespread clinical application for brain tumor treatments [2, 3, 11]. A fundamental challenge to IA drug delivery is that drugs must be extracted efficiently as they transit rapidly through a very well perfused tissue.…”

Section: Discussionmentioning

confidence: 99%

“…The ultra-fast first-pass kinetics of IA drug injections are beyond the temporal resolution of conventional pharmacokinetic methods, such as micro-dialysis and tissue biopsy [11]. Therefore, we used a specialized version of diffuse reflectance spectroscopy (DRS) to track brain tissue concentrations of cationic liposomes that were labeled with a near infrared dye, DilC 18 (7) [12–14].…”

Section: Introductionmentioning

confidence: 99%

Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue

et al. 2014

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Object Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (< 3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Methods Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery vs. intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain four hours after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. Results IA injections of cationic liposomes during TCH increased their delivery approximately four-fold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue four hours after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Conclusions Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 hours after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH.

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Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders

Seras‐Franzoso

Díaz‐Riascos

Corchero

et al. 2021

J of Extracellular Vesicle

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In the present study the use of extracellular vesicles (EVs) as vehicles for therapeutic enzymes in lysosomal storage disorders was explored. EVs were isolated from mammalian cells overexpressing alpha-galactosidase A (GLA) or N-sulfoglucosamine sulfohydrolase (SGSH) enzymes, defective in Fabry and Sanfilippo A diseases, respectively. Direct purification of EVs from cell supernatants was found to be a simple and efficient method to obtain highly active GLA and SGSH proteins, even after EV lyophilization. Likewise, EVs carrying GLA (EV-GLA) were rapidly uptaken and reached the lysosomes in cellular models of Fabry disease, restoring lysosomal functionality much more efficiently than the recombinant enzyme in clinical use. In vivo, EVs were well tolerated and distributed among all main organs, including the brain. DiR-labelled EVs were localized in brain parenchyma 1 h after intra-arterial (internal carotid artery) or intravenous (tail vein) administrations. Moreover, a single intravenous administration of EV-GLA was able to reduce globotriaosylceramide

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Intracarotid Delivery of Drugs

Cited by 56 publications

References 156 publications

Cerebral Hypoperfusion-Assisted Intra-arterial Deposition of Liposomes in Normal and Glioma-Bearing Rats

Cerebral Hypoperfusion-Assisted Intra-arterial Deposition of Liposomes in Normal and Glioma-Bearing Rats

Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue

Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders

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