Shape-specific microfabricated particles for biomedical applications: a review

Abstract

The storied history of controlled the release systems has evolved over time; from degradable drug-loaded sutures to monolithic zero-ordered release devices and nano-sized drug delivery formulations. Scientists have tuned the physico-chemical properties of these drug carriers to optimize their performance in biomedical/pharmaceutical applications. In particular, particle drug delivery systems at the micron size regime have been used since the 1980s. Recent advances in micro and nanofabrication techniques have enabled precise control of particle size and geometry–here we review the utility of microplates and discoidal polymeric particles for a range of pharmaceutical applications. Microplates are defined as micrometer scale polymeric local depot devices in cuboid form, while discoidal polymeric nanoconstructs are disk-shaped polymeric particles having a cross-sectional diameter in the micrometer range and a thickness in the hundreds of nanometer range. These versatile particles can be used to treat several pathologies such as cancer, inflammatory diseases and vascular diseases, by leveraging their size, shape, physical properties (e.g., stiffness), and component materials, to tune their functionality. This review highlights design and fabrication strategies for these particles, discusses their applications, and elaborates on emerging trends for their use in formulations. Graphical abstract

Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis

“…It is also important to observe that this prototypical formulation of RS504393 into µPLs provides a significant improvement in joint health despite the relatively low encapsulation efficiency. This appears to be in line with similar drug delivery systems previously developed for diverse medical applications by the authors [ 14 , 16 , 29 , 30 ] and with the commercially available ZILRETTA microparticles, returning a nominal drug load of 25% for the synthetic corticosteroid triamcinolone acetonide [ 31 , 32 ]. Indeed, a higher EE of up to 80% could be obtained by using drug conjugates, such as dexamethasone palmitate, as recently documented by Fattal and his group [ 33 ].…”

Matrix metalloproteinase responsive hydrogel microplates for programmed killing of invasive tumour cells

“…28 This allows for the formation of polymer nanoconstructs with a size and shape depending on the design of the silicon master template which is etched with a direct laser writing device, as previously reported. 21,[29][30][31][32][33] Further details of the templating process can be found in the ESI (Fig. S3).…”

Strategies for Targeted Delivery via Structurally Variant Polymeric Nanocarriers

“…The conventional phosphatidylcholine/cholesterol (PC/Chol) liposomes lack functional groups, viz., amine and carboxylic acid, which make it difficult to bind with protein receptors. Liang et al., have reported cationic polymeric liposomes based on octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol (OQCMC/Chol) with improved physico‐chemical characteristics compared to traditional liposomes [21,103] . The polymer‐liposomal surface could be modified with a trans‐activating transcriptional activator protein (TAT peptide), demonstrated uptake of both hydrophobic (oil‐soluble magnetic nanoparticles) and hydrophilic components (quantum dots), and exhibited encapsulation efficiency (∼90 %) of the anti‐cancer drug Vincristine compared to a conventional Phos/Chol.…”

“…[14] While non-spherical aggregates such as peptide based aggregates, [15] hydrogels [16,17] and carbon nanotubes [18][19][20] behave differently due to the altered interactions present, these have been recently paid attention to, as they resemble the behavioral characteristics of nonspherical moieties such as viruses, pathogens, erythrocytes, etc. [21,22] The size of the PNCs is another key factor determining the compartmentalization of drug and its in-vivo pharmacokinetics. The upper limit of the PNCs is generally restricted to 200 nm to avoid sedimentation and facilitate ease of movement within the body fluids.…”

“…Spherical nanoaggregates such as liposomes, [11] polymeric micelles, [12] dendrimers [13] etc., have therefore been extensively deployed as drug delivery tools [14] . While non‐spherical aggregates such as peptide based aggregates, [15] hydrogels [16,17] and carbon nanotubes [18–20] behave differently due to the altered interactions present, these have been recently paid attention to, as they resemble the behavioral characteristics of non‐spherical moieties such as viruses, pathogens, erythrocytes, etc [21,22] …”