Special Issue "Novel Approaches for Delivery of Anti-HIV Drugs"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (20 February 2019)

Special Issue Editor

Guest Editor
Dr. José Das Neves

Nanomedicines & Translational Drug Delivery, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
E-Mail
Interests: antiretroviral drug delivery; HIV prevention; microbicides; mucosal drug delivery; nanomedicine

Special Issue Information

Dear Colleagues,

HIV/AIDS continues to be one of the most challenging individual and public health concerns of our days, affecting roughly 37 million individuals worldwide and killing nearly two million people each year according to the UNAIDS (The Joint United Nations Programme on HIV/AIDS). Investments in the field have been huge but a cure to the infection remains elusive. Nonetheless, tremendous advances have been made over the last 35 years since the HIV-1 was identified, namely in prevention, diagnostics and treatment. The development of antiretroviral drugs and the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s—currently referred to as combination antiretroviral therapy (cART)—led to a dramatic shift of AIDS from a fatal disease into a chronic and often stable medical condition. In fact, cART contributed decisively to a steady decrease in the number of HIV-related deaths since the first years of the new millennium. Antiretroviral drugs have also been found useful in the prevention field, particularly in post-exposure prophylaxis (PEP) or mother-to-child transmission. Treatment as prevention and pre-exposure prophylaxis (PrEP) have further contributed to the reduction of sexually-transmitted HIV infections. Long-lasting injectable products and antiretroviral-based microbicides that are currently in late stages of clinical development or regulatory approval may soon provide new options for prevention. Gene therapy and the use of broadly neutralizing antibodies is also attracting a great deal of interest as possible approaches to HIV/AIDS management.

Still, many challenges remain in anti-HIV drug therapy/prophylaxis and these include, among others: (i) the onset of severe adverse effects leading to discontinuation or interruption of therapy/prophylaxis; (ii) sub-optimal biodistribution and pharmacokinetics, particularly at reservoir sites or mucosae involved in sexual transmission; (iii) the occurrence of viral resistance; (iv) troublesome regimens and/or drug delivery routes that lead to poor adherence by patients/users; (v) low stability and reduced shelf-life of active molecules, which may be particularly challenging in tropical climates and low-resource regions lacking adequate refrigerated distribution channels and storage; (vi) lack of adequate dosage forms for particular populations (e.g. children, women); (vii) costly drug products that are often inaccessible to populations in need of therapy/prophylaxis; and (viii) social and legal constraints resulting in poor access to and discontinuation of anti-HIV therapy/prophylaxis.

This Special Issue of Pharmaceutics intends to focus on new strategies and approaches to the formulation and delivery of anti-HIV drugs (including genetic material and other biopharmaceuticals), which could help solving many of the above identified issues. We welcome articles on all aspects of anti-HIV drug delivery intended at advancing therapy or prophylaxis of HIV/AIDS.

Dr. José das Neves
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Acquired Immunodeficiency Syndrome (AIDS)
  • Anti-HIV Agents
  • Antiretroviral Drug Delivery
  • Broadly Neutralizing Antibodies
  • Combination Antiretroviral Therapy (cART)
  • Combination Products
  • Gene Therapy
  • Human Immunodeficiency Virus (HIV)
  • Long Acting Injectables
  • Microbicide Vaginal Rings
  • Mother-To-Child Transmission
  • Multipurpose Prevention Technologies
  • Nanomedicines
  • NeuroAIDS
  • Pharmacokinetics
  • Post-Exposure Prophylaxis (PEP)
  • Pre-Exposure Prophylaxis (PrEP)
  • Rectal Microbicides
  • Reservoir Sites
  • Vaginal Microbicides

Published Papers (8 papers)

View options order results:
result details:
Displaying articles 1-8
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Design of Poly(lactic-co-glycolic Acid) (PLGA) Nanoparticles for Vaginal Co-Delivery of Griffithsin and Dapivirine and Their Synergistic Effect for HIV Prophylaxis
Pharmaceutics 2019, 11(4), 184; https://doi.org/10.3390/pharmaceutics11040184
Received: 21 February 2019 / Revised: 3 April 2019 / Accepted: 11 April 2019 / Published: 16 April 2019
PDF Full-text (4037 KB) | HTML Full-text | XML Full-text
Abstract
Long-acting topical products for pre-exposure prophylaxis (PrEP) that combine antiretrovirals (ARVs) inhibiting initial stages of infection are highly promising for prevention of HIV sexual transmission. We fabricated core-shell poly(lactide-co-glycolide) (PLGA) nanoparticles, loaded with two potent ARVs, griffithsin (GRFT) and dapivirine (DPV), [...] Read more.
Long-acting topical products for pre-exposure prophylaxis (PrEP) that combine antiretrovirals (ARVs) inhibiting initial stages of infection are highly promising for prevention of HIV sexual transmission. We fabricated core-shell poly(lactide-co-glycolide) (PLGA) nanoparticles, loaded with two potent ARVs, griffithsin (GRFT) and dapivirine (DPV), having different physicochemical properties and specifically targeting the fusion and reverse transcription steps of HIV replication, as a potential long-acting microbicide product. The nanoparticles were evaluated for particle size and zeta potential, drug release, cytotoxicity, cellular uptake and in vitro bioactivity. PLGA nanoparticles, with diameter around 180–200 nm, successfully encapsulated GRFT (45% of initially added) and DPV (70%). Both drugs showed a biphasic release with initial burst phase followed by a sustained release phase. GRFT and DPV nanoparticles were non-toxic and maintained bioactivity (IC50 values of 0.5 nM and 4.7 nM, respectively) in a cell-based assay. The combination of drugs in both unformulated and encapsulated in nanoparticles showed strong synergistic drug activity at 1:1 ratio of IC50 values. This is the first study to co-deliver a protein (GRFT) and a hydrophobic small molecule (DPV) in PLGA nanoparticles as microbicides. Our findings demonstrate that the combination of GRFT and DPV in nanoparticles is highly potent and possess properties critical to the design of a sustained release microbicide. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Figure 1

Open AccessArticle
Development of a Transdermal Delivery System for Tenofovir Alafenamide, a Prodrug of Tenofovir with Potent Antiviral Activity Against HIV and HBV
Pharmaceutics 2019, 11(4), 173; https://doi.org/10.3390/pharmaceutics11040173
Received: 27 February 2019 / Revised: 2 April 2019 / Accepted: 3 April 2019 / Published: 9 April 2019
PDF Full-text (3310 KB) | HTML Full-text | XML Full-text
Abstract
Tenofovir alafenamide (TAF) is an effective nucleotide reverse transcriptase inhibitor that is used in the treatment of HIV-1 and HBV. Currently, it is being investigated for HIV prophylaxis. Oral TAF regimens require daily intake, which hampers adherence and increases the possibility of viral [...] Read more.
Tenofovir alafenamide (TAF) is an effective nucleotide reverse transcriptase inhibitor that is used in the treatment of HIV-1 and HBV. Currently, it is being investigated for HIV prophylaxis. Oral TAF regimens require daily intake, which hampers adherence and increases the possibility of viral resistance. Long-acting formulations would significantly reduce this problem. Therefore, the aim of this study was to develop a transdermal patch containing TAF and investigate its performance in vitro through human epidermis. Two types of TAF patches were manufactured. Transparent patches were prepared using acrylate adhesive (DURO-TAK 87-2516), and suspension patches were prepared using silicone (BIO-PSA 7-4301) and polyisobutylene (DURO-TAK 87-6908) adhesives. In vitro permeation studies were performed while using vertical Franz diffusion cells for seven days. An optimized silicone-based patch was characterized for its adhesive properties and tested for skin irritation. The acrylate-based patches, comprising 2% w/w TAF and a combination of chemical enhancers, showed a maximum flux of 0.60 ± 0.09 µg/cm2/h. However, the silicone-based patch comprising of 15% w/w TAF showed the highest permeation (7.24 ± 0.47 μg/cm2/h). This study demonstrates the feasibility of developing silicone-based transdermal patches that can deliver a therapeutically relevant dose of TAF for the control of HIV and HBV infections. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Graphical abstract

Open AccessArticle
Tenofovir Hot-Melt Granulation using Gelucire® to Develop Sustained-Release Vaginal Systems for Weekly Protection against Sexual Transmission of HIV
Pharmaceutics 2019, 11(3), 137; https://doi.org/10.3390/pharmaceutics11030137
Received: 15 February 2019 / Revised: 12 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
PDF Full-text (4793 KB) | HTML Full-text | XML Full-text
Abstract
Hot-melt granulation is a technique used to obtain granules by dispersing a drug in polymers at a high temperature. Tenofovir, an antiretroviral drug with proven activity as a vaginal microbicide, was dispersed in melted Gelucire® (or a mixture of different Gelucire® [...] Read more.
Hot-melt granulation is a technique used to obtain granules by dispersing a drug in polymers at a high temperature. Tenofovir, an antiretroviral drug with proven activity as a vaginal microbicide, was dispersed in melted Gelucire® (or a mixture of different Gelucire®) to obtain drug-loaded granules. Studies performed on the granules proved that the drug is not altered in the hot-melt granulation process. The granules obtained were included in a matrix formed by the hydrophilic polymers hydroxypropylmethylcellulose and chitosan to obtain vaginal tablets that combine different mechanisms of controlled release: The Gelucire® needs to soften to allow the release of the Tenofovir, and the hydrophilic polymers must form a gel so the drug can diffuse through it. The studies performed with the tablets were swelling behavior, Tenofovir release, and ex vivo mucoadhesion. The tablets containing granules obtained with Tenofovir and Gelucire® 43/01 in a ratio of 1:2 in a matrix formed by hydroxypropylmethylcellulose and chitosan in a ratio of 1.9:1 were selected as the optimal formulation, since they release Tenofovir in a sustained manner over 216h and remain attached to the vaginal mucosa throughout. A weekly administration of these tablets would therefore offer women protection against the sexual transmission of HIV. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Graphical abstract

Review

Jump to: Research

Open AccessReview
Eradication of Human Immunodeficiency Virus Type-1 (HIV-1)-Infected Cells
Pharmaceutics 2019, 11(6), 255; https://doi.org/10.3390/pharmaceutics11060255
Received: 12 March 2019 / Revised: 1 May 2019 / Accepted: 24 May 2019 / Published: 1 June 2019
PDF Full-text (2194 KB) | HTML Full-text | XML Full-text
Abstract
Predictions made soon after the introduction of human immunodeficiency virus type-1 (HIV-1) protease inhibitors about potentially eradicating the cellular reservoirs of HIV-1 in infected individuals were too optimistic. The ability of the HIV-1 genome to remain in the chromosomes of resting CD4+ T [...] Read more.
Predictions made soon after the introduction of human immunodeficiency virus type-1 (HIV-1) protease inhibitors about potentially eradicating the cellular reservoirs of HIV-1 in infected individuals were too optimistic. The ability of the HIV-1 genome to remain in the chromosomes of resting CD4+ T cells and macrophages without being expressed (HIV-1 latency) has prompted studies to activate the cells in the hopes that the immune system can recognize and clear these cells. The absence of natural clearance of latently infected cells has led to the recognition that additional interventions are necessary. Here, we review the potential of utilizing suicide gene therapy to kill infected cells, excising the chromosome-integrated HIV-1 DNA, and targeting cytotoxic liposomes to latency-reversed HIV-1-infected cells. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Figure 1

Open AccessReview
Reverse Transcriptase Inhibitors Nanosystems Designed for Drug Stability and Controlled Delivery
Pharmaceutics 2019, 11(5), 197; https://doi.org/10.3390/pharmaceutics11050197
Received: 20 March 2019 / Revised: 12 April 2019 / Accepted: 22 April 2019 / Published: 27 April 2019
PDF Full-text (1333 KB) | HTML Full-text | XML Full-text
Abstract
An in-depth analysis of nanotechnology applications for the improvement of solubility, distribution, bioavailability and stability of reverse transcriptase inhibitors is reported. Current clinically used nucleoside and non-nucleoside agents, included in combination therapies, were examined in the present survey, as drugs belonging to these [...] Read more.
An in-depth analysis of nanotechnology applications for the improvement of solubility, distribution, bioavailability and stability of reverse transcriptase inhibitors is reported. Current clinically used nucleoside and non-nucleoside agents, included in combination therapies, were examined in the present survey, as drugs belonging to these classes are the major component of highly active antiretroviral treatments. The inclusion of such agents into supramolecular vesicular systems, such as liposomes, niosomes and lipid solid NPs, overcomes several drawbacks related to the action of these drugs, including drug instability and unfavorable pharmacokinetics. Overall results reported in the literature show that the performances of these drugs could be significantly improved by inclusion into nanosystems. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Graphical abstract

Open AccessReview
Relating Advanced Electrospun Fiber Architectures to the Temporal Release of Active Agents to Meet the Needs of Next-Generation Intravaginal Delivery Applications
Pharmaceutics 2019, 11(4), 160; https://doi.org/10.3390/pharmaceutics11040160
Received: 7 March 2019 / Revised: 28 March 2019 / Accepted: 30 March 2019 / Published: 3 April 2019
PDF Full-text (2571 KB) | HTML Full-text | XML Full-text
Abstract
Electrospun fibers have emerged as a relatively new delivery platform to improve active agent retention and delivery for intravaginal applications. While uniaxial fibers have been explored in a variety of applications including intravaginal delivery, the consideration of more advanced fiber architectures may offer [...] Read more.
Electrospun fibers have emerged as a relatively new delivery platform to improve active agent retention and delivery for intravaginal applications. While uniaxial fibers have been explored in a variety of applications including intravaginal delivery, the consideration of more advanced fiber architectures may offer new options to improve delivery to the female reproductive tract. In this review, we summarize the advancements of electrospun coaxial, multilayered, and nanoparticle-fiber architectures utilized in other applications and discuss how different material combinations within these architectures provide varied durations of release, here categorized as either transient (within 24 h), short-term (24 h to one week), or sustained (beyond one week). We seek to systematically relate material type and fiber architecture to active agent release kinetics. Last, we explore how lessons derived from these architectures may be applied to address the needs of future intravaginal delivery platforms for a given prophylactic or therapeutic application. The overall goal of this review is to provide a summary of different fiber architectures that have been useful for active agent delivery and to provide guidelines for the development of new formulations that exhibit release kinetics relevant to the time frames and the diversity of active agents needed in next-generation multipurpose applications. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Graphical abstract

Open AccessReview
Pharmaceutical Vehicles for Vaginal and Rectal Administration of Anti-HIV Microbicide Nanosystems
Pharmaceutics 2019, 11(3), 145; https://doi.org/10.3390/pharmaceutics11030145
Received: 1 March 2019 / Revised: 18 March 2019 / Accepted: 22 March 2019 / Published: 26 March 2019
PDF Full-text (1940 KB) | HTML Full-text | XML Full-text
Abstract
Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but effective and safe products are yet to be approved and made available to those in need. While most [...] Read more.
Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but effective and safe products are yet to be approved and made available to those in need. While most efforts have been placed in finding and testing suitable active drug candidates to be used in microbicide development, the last decade also saw considerable advances in the design of adequate carrier systems and formulations that could lead to products presenting enhanced performance in protecting from infection. One strategy demonstrating great potential encompasses the use of nanosystems, either with intrinsic antiviral activity or acting as carriers for promising microbicide drug candidates. Polymeric nanoparticles, in particular, have been shown to be able to enhance mucosal distribution and retention of promising antiretroviral compounds. One important aspect in the development of nanotechnology-based microbicides relates to the design of pharmaceutical vehicles that allow not only convenient vaginal and/or rectal administration, but also preserve or even enhance the performance of nanosystems. In this manuscript, we revise relevant work concerning the selection of vaginal/rectal dosage forms and vehicle formulation development for the administration of microbicide nanosystems. We also pinpoint major gaps in the field and provide pertinent hints for future work. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Graphical abstract

Open AccessReview
Gene Therapy Approaches to Functional Cure and Protection of Hematopoietic Potential in HIV Infection
Pharmaceutics 2019, 11(3), 114; https://doi.org/10.3390/pharmaceutics11030114
Received: 7 February 2019 / Revised: 5 March 2019 / Accepted: 6 March 2019 / Published: 11 March 2019
PDF Full-text (1809 KB) | HTML Full-text | XML Full-text
Abstract
Although current antiretroviral drug therapy can suppress the replication of human immunodeficiency virus (HIV), a lifelong prescription is necessary to avoid viral rebound. The problem of persistent and ineradicable viral reservoirs in HIV-infected people continues to be a global threat. In addition, some [...] Read more.
Although current antiretroviral drug therapy can suppress the replication of human immunodeficiency virus (HIV), a lifelong prescription is necessary to avoid viral rebound. The problem of persistent and ineradicable viral reservoirs in HIV-infected people continues to be a global threat. In addition, some HIV-infected patients do not experience sufficient T-cell immune restoration despite being aviremic during treatment. This is likely due to altered hematopoietic potential. To achieve the global eradication of HIV disease, a cure is needed. To this end, tremendous efforts have been made in the field of anti-HIV gene therapy. This review will discuss the concepts of HIV cure and relative viral attenuation and provide an overview of various gene therapy approaches aimed at a complete or functional HIV cure and protection of hematopoietic functions. Full article
(This article belongs to the Special Issue Novel Approaches for Delivery of Anti-HIV Drugs)
Figures

Figure 1

Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top