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Review
. 2019 Aug 1;11(8):374.
doi: 10.3390/pharmaceutics11080374.

Topical Inserts: A Versatile Delivery Form for HIV Prevention

M Melissa Peet  1 , Vivek Agrahari  2 , Sharon M Anderson  2 , Homaira Hanif  2 , Onkar N Singh  2 , Andrea R Thurman  2 , Gustavo F Doncel  2 , Meredith R Clark  2
Affiliations
Review

Topical Inserts: A Versatile Delivery Form for HIV Prevention

M Melissa Peet et al. Pharmaceutics. .

Abstract

The development of topical inserts for the prevention of sexually transmitted infections (STIs), particularly human immunodeficiency virus (HIV), represents a promising alternative to oral and parenteral pre-exposure prophylaxis (PrEP) dosage forms. They may be used for vaginal and/or rectal administration of a variety of agents with antiviral activity. Topical inserts deliver drugs to the portal of viral entry, i.e., the genital or rectal mucosa, with low systemic exposure, and therefore are safer and have fewer side effects than systemic PrEP agents. They may dissolve fast, releasing the active drugs within minutes of insertion, or slowly for long-acting drug delivery. Furthermore, they are user-friendly being easy to administer, discreet and highly portable. They are also economical and easy to manufacture at scale and to distribute, with excellent stability and shelf-life. Altogether, topical inserts represent a particularly promising form of drug delivery for HIV and STI prevention. Highlighted within this review are end-user acceptability research dedicated to understanding preferred attributes for this form of drug delivery, advantages and disadvantages of the formulation platform options, considerations for their development, clinical assessment of select placebo prototypes, future directions, and the potential impact of this dosage form on the HIV prevention landscape.

Keywords: HIV; extended-release; fast-disintegrating; microbicides; on-demand; protection; rectal drug delivery; tablets; vaginal drug delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative images of topical inserts in development: (A) CONRAD’s Tenofovir Alafenamide Fumarate/Elvitegravir (TAF/EVG) insert, (B) CONRAD’s first generation insert, Tenofovir/Emtricitabine (TFV/FTC), (C) IPM’s DS003 vaginal tablet (photo courtesy of Jeremy Nuttall, IPM), (D) Population Council and PATH’s Griffithsin/Carrageenan (GRFT/CG) fast-dissolve insert (photo courtesy of Tom Zydowsky, The Population Council) [20], (E) Osel’s MucoCept Lactobacillus vaginal tablet (Reproduced from [21], under the terms of the CC BY 4.0 license), (F) prototype extended-release EVG osmotic insert, evaluated preclinically by CONRAD in collaboration with Patrick Kiser (Northwestern University, Evanston, IL, USA).
Figure 2
Figure 2
Schematic of the different processes of topical insert disintegration with the introduction of vaginal fluid. Surface erosion: (A) The size of the insert decreases as the surface disintegrates releasing drug. Bulk erosion: The size of the insert first increases due to fluid uptake and swelling, followed by (B) breakdown of the insert into smaller pieces until fully disintegrated or (C) transformation from the solid state into a gel.
Figure 3
Figure 3
Factors to consider during the design and development process of inserts.
Figure 4
Figure 4
Placebo vaginal inserts tested in CONRAD Study D15-134 [32].
See this image and copyright information in PMC

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