Safety, Tolerability, and Proof-Of-Concept Study of OKV-119, a Novel Exenatide Long-Term Drug Delivery System, in Healthy Cats

Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in glucose homeostasis and food intake. In people, GLP-1 receptor agonists (GLP-1RAs) are commonly used for the treatment of type 2 diabetes mellitus (DM) and obesity; however, non-adherence to injectable medications is common. OKV-119 is an investigational drug delivery system intended for subdermal implantation and delivery of the GLP-1RA exenatide for up to 6 months.Hypothesis/Objectives: Develop protocols for the subcutaneous (SC) insertion and removal of OKV-119 and to evaluate its tolerability, in vivo drug-releasing characteristics, and weight-loss effects in cats.Animals: Two cadaveric and 19 purpose-bred cats.Methods: In cadavers, OKV-119 insertion protocol and imaging were performed at three SC locations. The safety and tolerability of OKV-119 implants were assessed in a small (n = 4 cats) 62-day study. Weekly plasma exenatide concentrations and body weight were measured in a 42-day proof-of-concept study designed to evaluate OKV-119 prototypes implanted in cats (n = 15).Results: In anesthetized cats, the duration of insertion and removal procedures was 1–2 min. OKV-119 was easily identified on radiographs, and well-tolerated without any apparent implant site reactions. Following implantation, exanatide plasma concentrations were observed for up to 35 days. Plasma exenatide concentrations were correlated to weight loss.Conclusion and clinical importance: Our findings suggest that OKV-119 could be easily inserted and removed during a routine clinic visit and can be used to safely and effectively deliver exenatide. Future studies of OKV-119, configured to release exenatide for a longer extended months-long duration, are warranted to determine whether the combination of metabolic improvements and beneficial weight-loss, coupled with minimal impact on pet-owner's lifestyle, lead to improved outcomes for obese cats and feline DM patients.

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A potential long-acting bictegravir loaded nano-drug delivery system for HIV-1 infection: A proof-of-concept study

Antiviral Research ◽

10.1016/j.antiviral.2019.04.007 ◽

2019 ◽

Vol 167 ◽

pp. 83-88 ◽

Cited By ~ 11

Author(s):

Subhra Mandal ◽

Pavan Kumar Prathipati ◽

Michael Belshan ◽

Christopher J. Destache

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Proof Of Concept ◽

Concept Study ◽

Nano Drug Delivery ◽

Long Acting ◽

Hiv 1

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In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: An in vivo proof of concept

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2017.02.024 ◽

2017 ◽

Vol 521 (1-2) ◽

pp. 196-203 ◽

Cited By ~ 10

Author(s):

Anil B. Jindal ◽

Sagar S. Bachhav ◽

Padma V. Devarajan

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Proof Of Concept ◽

Viral Reservoirs ◽

Antiretroviral Drug ◽

Nano Drug Delivery

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Glucan particles as anti-inflammatory agent and drug delivery system for natural compounds in experimentally induced intestinal inflammation in vivo

10.1055/s-0037-1608375 ◽

2017 ◽

Author(s):

D Rotrekl ◽

Z Vochyánová ◽

L Paráková ◽

I Saloň ◽

P Šalamúnová ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Intestinal Inflammation ◽

Natural Compounds ◽

Inflammatory Agent ◽

Anti Inflammatory ◽

Experimentally Induced

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Development and Evaluation of Floating Pulsatile Drug Delivery System Using Meloxicam

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v7i04.10647 ◽

2017 ◽

Vol 7 (04) ◽

Author(s):

ShirishaG. Suddala ◽

S. K. Sahoo ◽

M. R. Yamsani

Keyword(s):

Rheumatoid Arthritis ◽

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Lag Time ◽

Oral Dosage ◽

Lag Phase ◽

Pulsatile Drug Delivery

Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro drug release studies, water uptake and erosion studies, floating behaviour and in vivo radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.

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