Minimally invasive microneedles for ocular drug delivery

Singh, Raghu Raj Thakur; Tekko, Ismaiel A.; McAvoy, Kathryn; McMillan, Hannah; Jones, David S.; Donnelly, Ryan F.

doi:10.1080/17425247.2016.1218460

Cited by 125 publications

(61 citation statements)

References 68 publications

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“…In recent years, the development of ocular drug delivery systems has undergone a paradigm shift to ameliorate their poor drug bioavailability and absorption [6–8]. Research has been carried out to develop an array of ophthalmic dosage forms: solutions, drops, suspensions, ointments, injections, emulsions, microspheres, liposomes, nanoparticles, implants, niosomes, pharmacosomes, inserts, minidiscs and contact lenses for the treatment of a wide range of ophthalmic disorders [9,10]. Figure 1 shows the anatomy of the human eye and the different routes of administration through which the above dosage forms are administered [11].…”

Section: Introductionmentioning

confidence: 99%

Physicochemical attributes and dissolution testing of ophthalmic ointments

Bao

Jog

Shen

et al. 2017

International Journal of Pharmaceutics

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The investigation of semisolid ophthalmic ointments is challenging due to their complex physicochemical properties and the unique anatomy of the human eye. Using Lotemax as a model ophthalmic ointment, three different manufacturing processes and two excipient sources (Fisher (OWP) and Fougera (NWP)) were used to prepare loteprednol etabonate ointments that were qualitatively and quantitatively the same across the manufactured formulations. Physicochemical properties including drug content and uniformity, particle size and distribution, as well as rheological parameters (onset point, crossover modulus, storage modulus and Power law consistency index) were investigated. In addition, USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the ophthalmic ointments. Both manufacturing processes and excipient sources had a significant influence on the physicochemical attributes and the in vitro drug release profiles of the prepared ointments. Ointments prepared via the hot melt processes exhibited higher rheological parameters and lower drug release rates compared to ointments prepared without hot melting. Ointments prepared with OWP demonstrated higher rheological parameters and lower in vitro drug release rates compared to ointments prepared with NWP. A strong correlation between the rheological parameters and in vitro drug release rate was shown using logarithmic linear regression. This correlation may be useful in predicting in vitro drug release from measured physicochemical properties, and identifying the critical quality attributes during the development of ointment formulations.

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Section: Introductionmentioning

confidence: 99%

Physicochemical attributes and dissolution testing of ophthalmic ointments

Bao

Jog

Shen

et al. 2017

International Journal of Pharmaceutics

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“…However, these devices were limited to a certain total drug dosage, not controllable, with a limited time of action and accidental loss. 15 In addition, microneedles that can be inserted into the cornea, [34][35][36] trans-corneal ultrasound-media drug delivery, 37 and trans-corneal iontophoresis techniques have been reported. [38][39][40] Even though these methods are non-invasive or minimally invasive, to increase the ability of the drug to travel across the biological barrier, and further research is required to confirm their safety and efficacy.…”

Section: Dovepressmentioning

confidence: 99%

<p>Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop</p>

Lin

Zhao

Huang

et al. 2020

DDDT

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Background: The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits. Methods: Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/ h up to 10 h and the same solution was administered at one drop (50 μL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1. Results: The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45±919.89 μg/g and 97.18±43.14 μg/g in cornea, 3033.92±1061.95 μg/g and 806.99 ±563.02 μg/g in conjunctiva, 1570.19±402.87 μg/g and 46.93±23.46 μg/g in iris, 181.94 ±47.11 μg/g and 15.38±4.00 μg/g in ciliary body, 29.78±4.90 μg/mL and 3.20±1.48 μg/mL in aqueous humour, and 26.89±5.57 μg/mL and 1.90±1.87 μg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p<0.05) in the CTOIDD group. The AUC 0-24 values in the CTOIDD group were 27,543.70 μg•h/g in cornea, 32,514.48 μg•h/g in conjunctiva, 8631.05 μg•h/g in iris, 2194.36 μg•h/g in ciliary body and 343.9 μg•h/mL in aqueous humour, which were higher than for the eye drop group in all tissues. Conclusion: Since continuous instillation of NVCM with CTOIDD could reach significantly higher concentrations and was sustained for a longer period compared with hourly administration of eye drop, CTOIDD administered NVCM could be a possible method to treat bacterial keratitis.

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“…MNs are minimally invasive devices consisting of needle‐like microprojections positioned on a baseplate (Thakur Singh et al, ). Upon insertion, the MNs pierce the tissue layers and deliver therapeutic agents directly to the intended ocular tissues such as cornea, sclera (Thakur et al, ), or suprachoroidal space (Gilger, Abarca, Salmon, & Patel, ; Y. C. Kim, Oh, Edelhauser, & Prausnitz, ) via minimally invasive and relatively more precise/reliable means than conventional needles.…”

Section: Ocular Drug Delivery Systemsmentioning

confidence: 99%

Fundamentals, challenges, and nanomedicine‐based solutions for ocular diseases

Srinivasarao

Lohiya

Katti

2018

WIREs Nanomed Nanobiotechnol

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The eye consists of sensitive, compactly adjoined tissue structures which act as strong physical (static) and physiological (dynamic) barriers that prevent entry of foreign bodies into the eye. Together, these barriers reduce the bioavailability of topically and intraocularly administered medicaments thus demanding frequent drug administration for the treatment of chronic eye diseases. Hence, development of drug delivery systems (DDS) that can be retained in ocular tissues for longer durations can help to reduce the frequency of drug administration, whereas, delivery systems that traverse through ocular barriers may offer higher bioavailability of administered drugs to otherwise inaccessible ocular tissues. These objectives can be partially/fully achieved using nanoparticulate/colloidal DDS. Colloidal DDS, due to their nanodimensions, undergo internalization by cells which enables transport of drugs through ocular barriers. Furthermore, nanoparticles can prolong duration of drug release and can increase residence time of entrapped cargo molecules in ocular tissues. Together, these aspects facilitate a higher bioavailability, prolonged therapeutic effect and reduced frequency of drug administration for the effective treatment of chronic ocular diseases. Hence, nanocarriers have been widely explored for ophthalmic drug delivery applications. In this review, we discuss the anatomy of ocular tissues along with their barrier properties. We then discuss ocular diseases along with the various routes of drug administration and pathways of drug transport in the eye. The next section discusses the influence of physicochemical properties of therapeutic molecules on their ocular distribution and conventional and advanced (nanoparticulate/colloidal DDS) drug formulations that are used for the treatment of ocular diseases.

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Minimally invasive microneedles for ocular drug delivery

Cited by 125 publications

References 68 publications

Physicochemical attributes and dissolution testing of ophthalmic ointments

Physicochemical attributes and dissolution testing of ophthalmic ointments

<p>Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop</p>

Fundamentals, challenges, and nanomedicine‐based solutions for ocular diseases

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