Approaches for CNS delivery of drugs – nose to brain targeting of antiretroviral agents as a potential attempt for complete elimination of major reservoir site of HIV to aid AIDS treatment

Gupta, Shweta; Kesarla, Rajesh; Omri, Abdelwahab

doi:10.1080/17425247.2019.1583206

Cited by 24 publications

(13 citation statements)

References 82 publications

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“…Infection of the CNS due to the human immunodeficiency virus (HIV) can lead to various complications including HIV-1-associated neurological disorders. 1,2 Thus, CNS delivery of anti-HIV agents is of great importance. The low bioavailability and poor permeability of the BBB are problematic when delivering anti-HIV agents to the CNS but to compound the situation, HIV-infected cells can act as reservoirs in the CNS and can be reactivated later.…”

Section: Introductionmentioning

confidence: 99%

<p>Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation</p>

Hosny¹

2020

IJN

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Background: Low bioavailability and poor permeability of the blood-brain barrier are problematic when delivering therapeutic agents and particularly anti-human immunodeficiency virus therapy to the central nervous system. The intranasal route offers an alternative for central nervous system delivery. Cubosomes have been reported as helpful vehicles for intranasal delivery of therapeutics to enable brain targeting. Objective: In this study, we aimed to develop the intranasal cubosomal thermogelling dispersion of saquinavir mesylate for central nervous system delivery. Methods: The Box-Behnken design was applied to study the effect of monoolein, Poloxamer 407, and polyvinyl alcohol as independent factors and the particle size, entrapment efficiency, gelation temperature, and stability index as responses. The optimized cubosomes were evaluated using transmission electron microscopy, ex vivo permeation, and in vivo pharmacokinetics. Results: The optimized formula consisting of monoolein (8.96%), Poloxamer 407 (17.45%), and polyvinyl alcohol (7.5%) was prepared and evaluated. Higher values for the steady-state flux, permeability coefficient, and enhancement factor were observed for the cubosomal thermogelling dispersion of saquinavir during ex vivo permeation in comparison with an aqueous suspension of saquinavir. From the pharmacokinetic profile, the relative bioavailability for the intranasal optimized formula was approximately 12-fold higher when compared with oral aqueous suspension and 2.5-fold greater when compared to the intranasal aqueous suspension of saquinavir. Conclusion: Overall, the saquinavir-loaded cubosomal thermogelling formulation is promising for central nervous system delivery by intranasal administration.

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Section: Introductionmentioning

confidence: 99%

<p>Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation</p>

Hosny¹

2020

IJN

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“…Drugs via nasal administration can be assimilated into the systemic circulation without enzyme degradation at a great lick and hepatic first-pass effect that is usually associated with oral administration, thereby enhancing the bioavailability and bringing about fleet onset of the pharmacological effect [80,81]. More importantly, nasal administration can allow direct delivery of many drugs into the CNS through the direct anatomical connection between the nasal cavity and the brain without crossing the BBB [82][83][84][85][86][87]. It is hypothesized that drugs deposited at the nasal mucosa mainly travel to the brain via the olfactory neurons and via the trigeminal nerves [85,88].…”

Section: Bypassing the Bbb With Noninvasive Approachesmentioning

confidence: 99%

“…More importantly, nasal administration can allow direct delivery of many drugs into the CNS through the direct anatomical connection between the nasal cavity and the brain without crossing the BBB [82][83][84][85][86][87]. It is hypothesized that drugs deposited at the nasal mucosa mainly travel to the brain via the olfactory neurons and via the trigeminal nerves [85,88]. The nose-to-brain delivery has been displayed in both preclinical and clinical studies with a variety of formulations such as nasal sprays, powders, gels, etc.…”

Section: Bypassing the Bbb With Noninvasive Approachesmentioning

confidence: 99%

Dendrimer-Based Drug Delivery Systems for Brain Targeting

2019

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Human neuroscience has made remarkable progress in understanding basic aspects of functional organization; it is a renowned fact that the blood–brain barrier (BBB) impedes the permeation and access of most drugs to central nervous system (CNS) and that many neurological diseases remain undertreated. Therefore, a number of nanocarriers have been designed over the past few decades to deliver drugs to the brain. Among these nanomaterials, dendrimers have procured an enormous attention from scholars because of their nanoscale uniform size, ease of multi-functionalization, and available internal cavities. As hyper-branched 3D macromolecules, dendrimers can be maneuvered to transport diverse therapeutic agents, incorporating small molecules, peptides, and genes; diminishing their cytotoxicity; and improving their efficacy. Herein, the present review will give exhaustive details of extensive researches in the field of dendrimer-based vehicles to deliver drugs through the BBB in a secure and effectual manner. It is also a souvenir in commemorating Donald A. Tomalia on his 80th birthday.

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“…This review discusses the potential of long-acting, tissue-targeting synthetic scaffolds that enable delivery of cART and HIV cure agents to HIV-burdened lymphatic tissues. Please refer to other excellent reviews for details on the penetration of nanotherapeutics into the central nervous system [9,10]. Particularly, this review will focus on how features from nanotechnology can aid in overcoming some of the key challenges faced by both cART and HIV cure strategies, including low bioavailability, low tissue penetration in lymphatic tissues and short plasma half-lives.…”

Section: Introductionmentioning

confidence: 99%

The Potential of Long-Acting, Tissue-Targeted Synthetic Nanotherapy for Delivery of Antiviral Therapy Against HIV Infection

Andersen

Tolstrup

2020

Viruses

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Oral administration of a combination of two or three antiretroviral drugs (cART) has transformed HIV from a life-threatening disease to a manageable infection. However, as the discontinuation of therapy leads to virus rebound in plasma within weeks, it is evident that, despite daily pill intake, the treatment is unable to clear the infection from the body. Furthermore, as cART drugs exhibit a much lower concentration in key HIV residual tissues, such as the brain and lymph nodes, there is a rationale for the development of drugs with enhanced tissue penetration. In addition, the treatment, with combinations of multiple different antiviral drugs that display different pharmacokinetic profiles, requires a strict dosing regimen to avoid the emergence of drug-resistant viral strains. An intriguing opportunity lies within the development of long-acting, synthetic scaffolds for delivering cART. These scaffolds can be designed with the goal to reduce the frequency of dosing and furthermore, hold the possibility of potential targeting to key HIV residual sites. Moreover, the synthesis of combinations of therapy as one molecule could unify the pharmacokinetic profiles of different antiviral drugs, thereby eliminating the consequences of sub-therapeutic concentrations. This review discusses the recent progress in the development of long-acting and tissue-targeted therapies against HIV for the delivery of direct antivirals, and examines how such developments fit in the context of exploring HIV cure strategies.

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Approaches for CNS delivery of drugs – nose to brain targeting of antiretroviral agents as a potential attempt for complete elimination of major reservoir site of HIV to aid AIDS treatment

Cited by 24 publications

References 82 publications

<p>Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation</p>

<p>Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation</p>

Dendrimer-Based Drug Delivery Systems for Brain Targeting

The Potential of Long-Acting, Tissue-Targeted Synthetic Nanotherapy for Delivery of Antiviral Therapy Against HIV Infection

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