A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis.

PURPOSE: The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by long acting drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. METHODS: A thin-film polycaprolactone (PCL) membrane controls drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. RESULTS: The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5 to 4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at <2.8 mg/day. Prototype devices demonstrated linear release at 1.2 mg/day for up to 90 days and at 2.2 mg/day for up to 60 days. CONCLUSIONS: We present a biodegradable TFPD for subcutaneous delivery of TAF for HIV PrEP. The size, shape and release rate of the device are tunable over a >8-fold range.

Fabrication of micropatterned polymeric nanowire arrays for high-resolution reagent localization and topographical cellular control.

Herein, we present a novel approach for the fabrication of micropatterned polymeric nanowire arrays that addresses the current need for scalable and customizable polymer nanofabrication. We describe two variations of this approach for the patterning of nanowire arrays on either flat polymeric films or discrete polymeric microstructures and go on to investigate biological applications for the resulting polymeric features. We demonstrate that the micropatterned arrays of densely packed nanowires facilitate rapid, low-waste drug and reagent localization with micron-scale resolution as a result of their high wettability. We also show that micropatterned nanowire arrays provide hierarchical cellular control by simultaneously directing cell shape on the micron scale and influencing focal adhesion formation on the nanoscale. This nanofabrication approach has potential applications in scaffold-based cellular control, biological assay miniaturization, and biomedical microdevice technology.

Methadone Treatment Gap in Tennessee and How Medication Units Could Bridge the Gap: A Review.

The opioid epidemic has been an ongoing public health concern in the United States (US) for the last few decades. The number of overdose deaths involving opioids, hereafter referred to as overdose deaths, has increased yearly since the mid-1990s. One treatment modality for opioid use disorder (OUD) is medication-assisted treatment (MAT). As of 2022, only three pharmacotherapy options have been approved by the Food and Drug Administration (FDA) for treating OUD: buprenorphine, methadone, and naltrexone. Unlike buprenorphine and naltrexone, methadone dispensing and administrating are restricted to opioid treatment programs (OTPs). To date, Tennessee has no medication units, and administration and dispensing of methadone is limited to licensed OTPs. This review details the research process used to develop a policy draft for medication units in Tennessee. This review is comprised of three parts: (1) a rapid review aimed at identifying obstacles and facilitators to OTP access in the US, (2) a descriptive analysis of Tennessee's geographic availability of OTPs, pharmacies, and federally qualified health centers (FQHCs), and (3) policy mapping of 21 US states' OTP regulations. In the rapid review, a total of 486 articles were imported into EndNote from PubMed and Embase. After removing 152 duplicates, 357 articles were screened based on their title and abstract. Thus, 34 articles underwent a full-text review to identify articles that addressed the accessibility of methadone treatment for OUD. A total of 18 articles were identified and analyzed. A descriptive analysis of Tennessee's availability of OTP showed that the state has 22 OTPs. All 22 OTPs were matched to a county and a region based on their address resulting in 15 counties (16%) and all three regions having at least one OTP. A total of 260 FQHCs and 2294 pharmacies are in Tennessee. Each facility was matched to a county based on its address resulting in 70 counties (74%) having at least one FQHC and 94 counties (99%) having at least one pharmacy. As of 31 December 2022, 17 states mentioned medication units in their state-level OTP regulations. Utilizing the regulations for the eleven states with medication units and federal guidelines, a policy draft was created for Tennessee's medication units.

Community-Centered Patient Journey Map in Opioid Use Disorder: A Tool to Address Compassion Fatigue among Community Pharmacists.

Community pharmacists have become increasingly exposed to opioid use disorders in recent decades. However, both pharmacist training and traditional practice environments have not been adequate to prepare the pharmacist for both the patient care needs and regulatory barriers of patients experiencing opioid use disorders (OUD). As a result, there is a need to increase pharmacists' awareness of both the overall patient experience as they navigate their OUD and the role of the community pharmacy as a touchpoint within that experience. To this end, a Community-Centered Patient Journey in Drug Addiction Treatment journey map was developed with expert insights, clinical experience, and in-depth interviews (conducted in spring of 2021) with 16 participants enrolled in licensed opioid treatment programs in Tennessee. Patients, policymakers, clinicians, and academic researchers were involved in the map development. Lived experiences of key informants were captured via in-depth interviews. A consensus decision-making approach was used throughout the patient journey map development process. The final patient journey map illustrates a non-linear pathway, describes the central role of the patient's community, and emphasizes three major "pain points" within the system (access, adherence, and affordability). Future research should investigate the impact of such a journey map on pharmacy personnel's knowledge, attitudes, and behaviors.

Patient reported goals for medications for opioid use disorder: A theory of proximal goal attainment.

Background: There exist substantial patient barriers to accessing medications for opioid use disorder (MOUD), including travel distance, stigma, and availability of MOUD providers. Yet, despite these barriers, there exists a subset of patients who possess the requisite motivation to seek and remain adherent to treatment. Objective: To explore patient-derived goals in MOUD treatment-adherent patients. Methods: This study used in-depth interviews with patients receiving methadone who were enrolled in opioid treatment programs (OTPs) across Tennessee. Participants were recruited from 12 different OTPs to participate in telephonic semi-structured interviews to a point of saturation. Participants had to be adherent to treatment, in treatment for 6 months or greater, and English speaking. Analysis occurred inductively using a constructivist approach to Grounded Theory. Results: In total, 17 patient interviews were conducted in the spring of 2021. Participants described goal setting across three general stages of treatment: (1) addressing acute physical and emotional needs upon treatment entry, (2) development of supportive structure and routine to develop healthy skills facilitated by treatment team, and (3) identifying and pursuing future-focused goals not directly linked to treatment. A Proximal Goals in MOUD Framework is introduced. Conclusion: In this qualitative study on patient reported goals in MOUD it was found that goals are transitory and relative to the stage of treatment. Further research is needed to better understand goal evolution over the course of treatment and its impact on treatment retention.

Device design methodology and formulation of a protein therapeutic for sustained release intraocular delivery.

Despite years of effort, sustained delivery of protein therapeutics remains an unmet need due to three primary challenges - dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir-based thin film devices suitable for long-acting protein delivery to the back of the eye. First, the challenge of formulating highly concentrated protein in a device reservoir was addressed by improving stability with solubility-reducing excipients. Next, predictive correlations between design parameters and device performance were developed to provide a methodology to achieve a target product profile. Prototype devices were designed using this methodology to achieve desired device size, release rate, therapeutic payload, and protein stability, assessed by in vitro studies. Finally, prototype tolerability was established in a non-human primate model. The design methodology presented here is widely applicable to reservoir-based sustained delivery devices for proteins and provides a general device design framework.

Development and Implementation of Tennessee Nonresidential Buprenorphine Treatment Guidelines.

OBJECTIVE: To describe the recent legislation in Tennessee and subsequent development and implementation of state-wide buprenorphine treatment guidelines. PRACTICE INNOVATION: In 2016, Tennessee began licensing office-based opioid treatment (OBOT) clinics. Due to initial licensing criteria, not all providers were required to be licensed with the Department of Mental Health and Substance Abuse Services (TDMHSAS). The gap in licensing made it difficult to ensure an appropriate standard of care was being met by all addiction treatment providers. Therefore, the state developed legislation that allowed for the creation of best practice guidelines to encompass all providers of buprenorphine in the state of Tennessee, not just the licensed OBOT clinics. The guidelines define what the standard of care should entail while treating this vulnerable addiction population. RESULTS: Tennessee legislation granted the formation of a committee to create the Tennessee Nonresidential Buprenorphine Treatment Guidelines. The committee was comprised of physicians, pharmacists, lawyers, law enforcement, and state officials. The finalized guidelines were published and effective January 1, 2018, and adopted as policy by the boards of medical examiners, osteopathic examination, and pharmacy shortly thereafter. The guidelines are now enforceable by the boards and give them the ability to discipline physicians who practice outside the standard of care. CONCLUSION: Tennessee legislation provides a model for other states to take action in combating this opioid crisis by not only increasing access to addiction treatment, but increasing access to quality care.

Probing the luminal microenvironment of reconstituted epithelial microtissues.

Polymeric microparticles can serve as carriers or sensors to instruct or characterize tissue biology. However, incorporating microparticles into tissues for in vitro assays remains a challenge. We exploit three-dimensional cell-patterning technologies and directed epithelial self-organization to deliver microparticles to the lumen of reconstituted human intestinal microtissues. We also develop a novel pH-sensitive microsensor that can measure the luminal pH of reconstituted epithelial microtissues. These studies offer a novel approach for investigating luminal microenvironments and drug-delivery across epithelial barriers.

Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery.

Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered.

Polycaprolactone thin-film drug delivery systems: Empirical and predictive models for device design.

PURPOSE: To define empirical models and parameters based on theoretical equations to describe drug release profiles from two polycaprolactone thin-film drug delivery systems. Additionally, to develop a predictive model for empirical parameters based on drugs' physicochemical properties. METHODS: Release profiles from a selection of drugs representing the standard pharmaceutical space in both polycaprolactone matrix and reservoir systems were determined experimentally. The proposed models were used to calculate empirical parameters describing drug diffusion and release. Observed correlations between empirical parameters and drug properties were used to develop equations to predict parameters based on drug properties. Predictive and empirical models were evaluated in the design of three prototype devices: a levonorgestrel matrix system for on-demand locally administered contraception, a timolol-maleate reservoir system for glaucoma treatment, and a primaquine-bisphosphate reservoir system for malaria prophylaxis. RESULTS: Proposed empirical equations accurately fit experimental data. Experimentally derived empirical parameters show significant correlations with LogP, molecular weight, and solubility. Empirical models based on predicted parameters accurately predict experimental release data for three prototype systems, demonstrating the accuracy and utility of these models. CONCLUSION: The proposed empirical models can be used to design polycaprolactone thin-film devices for target geometries and release rates. Empirical parameters can be predicted based on drug properties. Together, these models provide tools for preliminary evaluation and design of controlled-release delivery systems.