RESUMO
Microneedles (MN) have emerged as an innovative technology for drug delivery, offering a minimally invasive approach to administer therapeutic agents. Recent applications have included ocular drug delivery, requiring the manufacture of sub-millimeter needle arrays in a reproducible and reliable manner. The development of 3D printing technologies has facilitated the fabrication of MN via mold production, although there is a paucity of information available regarding how the printing parameters may influence crucial issues such as sharpness and penetration efficacy. In this study, we have developed and optimized a 3D-printed MN micro-mold using stereolithography (SLA) 3D printing to prepare a dissolving ocular MN system. The effects of a range of parameters including aspect ratio, layer thickness, length, mold shape and printing orientation have been examined with regard to both architecture and printing accuracy of the MN micro-mold, while the effects of printing angle on needle fidelity was also examined for a range of basic shapes (conical, pyramidal and triangular pyramidal). Mechanical strength and in vitro penetration of the polymeric (PVP/PVA) microneedles produced from reverse molds fabricated using MN with a range of shapes and height, and aspect ratios was assessed, followed by ex vivo studies of penetration into excised scleral and corneal tissue. The optimization process identified the parameters required to produce MN with the sharpest tips and highest dimensional fidelity, while the ex vivo studies indicated that these optimized systems would penetrate the ocular tissue with minimal applied pressure, thereby allowing ease of patient self-administration.
RESUMO
Cyclodextrin metal-organic frameworks (CD-MOF) are a class of biocompatible MOF with a great potential in drug delivery applications. Original CD-MOF crystals are fragile and large (0.2-1 mm), which are less useful in pharmaceutical applications. Cetyltrimethylammonium bromide and long chain poly(ethylene) glycol, used in size modulation to produce nanosized CD-MOF can compromise the biocompatibility, and physiochemical properties of CD-MOF as their complete removal from frameworks is difficult. To avoid the use of above-mentioned modulators, herein, we demonstrate the synthesis of nanosized CD-MOF using triethylamine (TEA) as a modulator to reduce their size to ~254 nm. The MOF characteristics such as crystal and chemical structure remain unaffected and the surface area of CD-MOF synthesised with TEA is measured 1075.5 m2/g, almost 50 % higher than those of synthesised using bulky modulators. The improved CD-MOF architecture utilized for the in-situ synthesis of silver nanoparticles resulted in enhanced antimicrobial efficacy tested against Staphylococcus aureus and Escherichia coli bacteria and Candida albicans fungus. And minimum inhibitory concentration (MIC) is recorded in the range of 31-15 µg/mL. Overall, the structural improvement in CD-MOF supported with thorough comparative investigations and enhanced antimicrobial efficacy could be very helpful in further establishing them in biomedicine field.
