Microneedles for drug delivery: trends and progress

In recent years there has been a surge in the research and development of microneedles, a transdermal delivery system that combines the technology of transdermal patches and hypodermic needles. The needles are in the hundreds of micron length range and therefore allow relatively little or no pain. For example, biodegradable microneedles have been researched in the literature and have several advantages compared to solid or hollow microneedles, as they produce non-sharp waste and can be designed to allow rapid or slow release of drugs. However they also pose a disadvantage as successful insertion into the stratum corneum layer of the skin relies on sufficient mechanical strength of the biodegradable material. This review looks at the various technologies developed in microneedle research and shows the rapidly growing numbers of research papers and patent publications since the first invention of microneedles (using time series statistical analysis). This provides the research and industry communities a valuable synopsis of the trends and progress being made in this field

Novel procedures for the production of multi-compartmental biodegradable polymeric Microneedles

The aim of this work is a new stamp based method to fabricate multi-compartmental polymeric microneedles containing a model drug

Enhancing the Transdermal Delivery of ‘Next Generation’ Variable New Antigen Receptors Using Microarray Patch Technology: a Proof-of-Concept Study

Heavy chain only binding proteins, such as variable new antigen receptors (VNARs), have emerged as an alternative to the highly successful therapeutic monoclonal antibodies (mAb). Owing to their small size (» 11 kDa)and single chain only architecture, they are amenable to modular reformatting and can be produced using inexpensive expression systems. Furthermore, due to their low molecular weight (MW) and high stability, theymay be suitable for alternative delivery strategies, such as microarray array patches (MAPs). In this study, thetransdermal delivery of ELN22-104, a multivalent anti-hTNF-a VNAR, was examined using both dissolving andhydrogel-forming MAPs. For dissolving MAPs, the cumulative in vitro permeation of ELN22-104 reached a plateau after 2 h (12.24 § 0.17 mg). This could be important for bolus dosing. Assessing two hydrogel-formingMAPs in vitro, PVP/PVA hydrogel-forming MAPs delivered significantly higher drug doses when compared to‘super swelling’ MAPs, equivalent to 43.13 § 10.36 mg and 23.13 § 5.66 mg, respectively (p < 0.05). Consequently, this study has proven that by modifying the MAP system, the transdermal delivery of a VNAR acrossthe skin can be enhanced. Furthermore, this proof-of-concept study has shown that transdermal delivery of‘next generation’ biotherapeutics is achievable using MAP technology

Formulation and Evaluation of Heparin Microneedle Transdermal Patch

The current use of anticoagulants is extensive and it was estimated that this multibillion dollar heparin market generated sales of high proportion. Unfortunately the need for repetitive parenteral administration is still major disadvantage. Low molecular weight heparin is high molecular weight hydrophilic polyanion with poor oral bioavailability and is hence administered parenterally. Poor oral absorption is due to ionic repulsion from negatively charged mucus and epithelial tissue, destruction by gastrointestinal bacteria and to lesser extent by the acidic condition of the stomach. Transdermal drug delivery is one potential solution to this problem. Skin is the largest organ of the human body, offers a painless and compliant interface for systemic drug administration. It provides sustained and controlled delivery over long periods with the feasibility of on demand termination and an attractive alternative to injections. It is evident that because of its large molecular weight, negative charge and hydrophilic nature passive transdermal delivery may not be feasible. In literature various attempts like ultrasoud, electric fields like electroporation and iontophoresis and combination of ultrasound and iontophoresis have been used to increase the permeation of LMWH. Each of these have limitations and hence in this study the use of microneedles were studied. Micro needles are tiny micron sixed structures that upon application can breach the stratum corneum (SC) and penetrate to the upper dermal layers. The delivery method is minimally invasive, pain free and has lot of potential for drug delivery across skin. Use of soluble microneedles which dissolve in the skin have been used in the present study. The purpose of this study was to develop a dissolving microneedle patch containing low molecular weight heparin with different ratios of polymers (PVP and PVA). In the present work, microneedle mold was prepared by using resin and hardner. The different ratio of Polyvinylalcohol and Polyvinylpyrrolidone (PVP K30) was prepared. The drug and polymer interaction was analysed by FTIR. The drug and polymer solution was poured in to the mold and dried and then peeled the drug loaded patch. The microneedle patch was analysed by Scanning electron microscopy, then evaluated the in vitro drug release, ex vivo permeation studies. It has been concluded that transdermal delivery of LMWH would allow easier compliance as compared to parenteral administration. However being a hydrophilic molecule it does not cross SC barrier and usage of enhancement strategies has limited value. It was observed that a more feasible approach would be the use of minimal invasive techniques like use of microneedles to breach the SC barrier. More research work is needed to enhance this research work to have animal study and human clinical trials carried out. Further work is to be carried out in order to determine its efficacy and safety by long term pharmacokinetic and pharmacodynamic studies in human beings and in vivo studies in human beings

Theranostic Gelatin Nanoparticles for Antigen Delivery and Combined Strategies for Transcutaneous Application

Transcutaneous application of vaccines is a promising strategy to enhance the effectiveness of vaccination using a reachable route of administration. Additionally, replacing the conventional needles with skin mechanical penetration techniques as microneedles or skin laser microporation will offer great advantages. This transcutaneous delivery techniques are pain-free and will help to avoid the hazards of needles. For the delivery of antigens, nanocarriers are so promising to enhance and modulate their immune response. The nanocarriers offer merits such as antigen protection from degradation, and controlling the release rate of the antigen. Additionally, due to the particulate nature of the nanocarriers, they can potentially display the antigen in a way that better mimics pathogens. For this aim, ovalbumin as a model antigen has been delivered using functionalized theranostic gelatin nanoparticles to bone marrow-derived dendritic cells (BMDCs). The nanoparticles were rendered fluorescent by using a novel imaging agent (gold and silver alloy nanoclusters) that emits near-infra red light. This was beneficial to study the nanoparticles uptake by BMDCs and also to image the nanoparticles within the skin tissue. Finally, the developed theranostic nanocarriers induced the maturation of the BMDCs and enhanced the proliferation of both helper T cells (CD4+) and cytotoxic T cells (CD8+). This indicates the potential efficacy of the delivery system for vaccination either against allergy or viruses and tumors

A compendium of current developments on polysaccharide and protein-based microneedles

Microneedles (MNs), i.e. minimally invasive three-dimensional microstructures that penetrate the stratum corneum inducing relatively little or no pain, have been studied as appealing therapeutic vehicles for transdermal drug delivery. Over the last years, the fabrication of MNs using biopolymers, such as polysaccharides and proteins, has sparked the imagination of scientists due to their recognized biocompatibility, biodegradability, ease of fabrication and sustainable character. Owing to their wide range of functional groups, polysaccharides and proteins enable the design and preparation of materials with tunable properties and functionalities. Therefore, these biopolymer-based MNs take a revolutionary step offering great potential not only in drug administration, but also in sensing and response to physiological stimuli. In this review, a critical and comprehensive overview of the polysaccharides and proteins employed in the design and engineering of MNs will be given. The strategies adopted for their preparation, their advantages and disadvantages will be also detailed. In addition, the potential and challenges of using these matrices to deliver drugs, vaccines and other molecules will be discussed. Finally, this appraisal ends with a perspective on the possibilities and challenges in research and development of polysaccharide and protein MNs, envisioning the future advances and clinical translation of these platforms as the next generation of drug delivery systems.publishe

Pharma-engineering of multifunctional microneedle array device for application in chronic pain

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within this thesis is the possibility of further developing transdermal drug delivery for chronic pain treatment using an Electro-Modulated Hydrogel- Microneedle array (EMHM) prototype device for the delivery of analgesic medicatio

Chitosan-graphene nanocomposite microneedle arrays for transdermal drug delivery

The project focused on the hypothesis that degradable, polymer microneedle arrays are a promising alternative to traditional drug delivery routes, offering the patient a painless, high concentration, and quick delivery of therapeutics through the skin. This project explored chitosan-graphene nanocomposites as potential materials for microneedle arrays; the addition of graphene to chitosan is believed to yield improved mechanical properties and electrical conductivity over pristine chitosan, which will allow for long and slender microneedles and for electrically stimulated drug delivery, and may positively affect the degradation and drug delivery properties of chitosan. Graphene derivatives, such as graphene oxide, reduced graphene oxide, graphene quantum dots, and magnetic graphene quantum dots were synthesised and then characterised, before they were used as the filler within chitosan nanocomposites. Their effect at varying concentrations upon the mechanical properties, electrical conductivity, drug release, and enzymatic degradation rate of chitosan were assessed. It was determined that reduced graphene oxide was the optimum nanoparticle to reinforce chitosan, achieving the best mechanical and electrical conductivity properties of the nanocomposites. Chitosan-graphene nanocomposite microneedle arrays were shown to passively release small molecular weight drugs at a high delivery quantity and rate. Conductive chitosan-graphene nanocomposite microneedles were tested to determine the effect of electrical stimulation on the release of large molecular weight drugs from the nanocomposite, with substantial improvements in the release rate of large molecular weight drugs when compared to passive diffusion. The microneedle arrays were shown to survive the force of insertion through compressive loading. The depth of penetration of the microneedles was determined through cross-sectional analysis of chicken skin