Treatment of Periodontal Infections, the Possible Role of Hydrogels as Antibiotic Drug-Delivery Systems.

With the advancement of biomedical research into antimicrobial treatments for various diseases, the source and delivery of antibiotics have attracted attention. In periodontal diseases, antibiotics are integral in positive treatment outcomes; however, the use of antibiotics is with caution as the potential for the emergence of resistant strains is of concern. Over the years, conventional routes of drug administration have been proven to be effective for the treatment of PD, yet the problem of antibiotic resistance to conventional therapies continues to remain a setback in future treatments. Hydrogels fabricated from natural and synthetic polymers have been extensively applied in biomedical sciences for the delivery of potent biological compounds. These polymeric materials either have intrinsic antibacterial properties or serve as good carriers for the delivery of antibacterial agents. The biocompatibility, low toxicity and biodegradability of some hydrogels have favoured their consideration as prospective carriers for antibacterial drug delivery in PD. This article reviews PD and its antibiotic treatment options, the role of bacteria in PD and the potential of hydrogels as antibacterial agents and for antibiotic drug delivery in PD. Finally, potential challenges and future directions of hydrogels for use in PD treatment and diagnosis are also highlighted.

Drug loaded implantable devices to treat cardiovascular disease.

INTRODUCTION: It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site. AREAS COVERED: In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant. EXPERT OPINION: Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.

The Role of Epigenetic and Biological Biomarkers in the Diagnosis of Periodontal Disease: A Systematic Review Approach.

The aim of this systemic review was to collate and analyze existing data from published literature sources to identify the current understanding of the role of epigenetic and biological biomarkers in periodontal disease and diagnostics. A comprehensive searching strategy was undertaken in Embase, Medline, The Dentistry and Oral Sciences and CINAHL databases. Grey literature searching strategies were also employed. Articles published in the English language between 2017−2020 were included. A total of 1014 studies were returned of which 15 studies were included. All included articles were cross-sectional, case−control studies. Relevant data were extracted according to various demographic and methodological factors including cohort size, oral biofluid sampled, number of examiners, smoking status and reported outcomes. A measure of the biomarker levels and corresponding significance were documented where possible. This review identified that exRNA has the greatest diagnostic potential, with four biomarkers (SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1) displaying sensitivity of >71% and specificity of 100% in the assessed samples (p < 0.001) for gingivitis. This work also identifies the need for a unified approach to future research to draw meaningful comparison. Further investigations are warranted to definitively validate exRNA data and for the development of an exRNA-specific point-of-care diagnostic test.

Enhancement strategies for transdermal drug delivery systems: current trends and applications.

Transdermal drug delivery systems have become an intriguing research topic in pharmaceutical technology area and one of the most frequently developed pharmaceutical products in global market. The use of these systems can overcome associated drawbacks of other delivery routes, such as oral and parenteral. The authors will review current trends, and future applications of transdermal technologies, with specific focus on providing a comprehensive understanding of transdermal drug delivery systems and enhancement strategies. This article will initially discuss each transdermal enhancement method used in the development of first-generation transdermal products. These methods include drug/vehicle interactions, vesicles and particles, stratum corneum modification, energy-driven methods and stratum corneum bypassing techniques. Through suitable design and implementation of active stratum corneum bypassing methods, notably microneedle technology, transdermal delivery systems have been shown to deliver both low and high molecular weight drugs. Microneedle technology platforms have proven themselves to be more versatile than other transdermal systems with opportunities for intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring. These have shown that microneedles have been a prospective strategy for improving transdermal delivery systems.

Medical Device Development for Children and Young People-Reviewing the Challenges and Opportunities.

Development of specific medical devices (MDs) is required to meet the healthcare needs of children and young people (CYP). In this context, MD development should address changes in growth and psychosocial maturation, physiology, and pathophysiology, and avoid inappropriate repurposing of adult technologies. Underpinning the development of MD for CYP is the need to ensure MD safety and effectiveness through pediatric MD-specific regulations. Contrary to current perceptions of limited market potential, the global pediatric healthcare market is expected to generate around USD 15,984 million by 2025. There are 1.8 billion young people in the world today; 40% of the global population is under 24, creating significant future healthcare market opportunities. This review highlights a number of technology areas that have led to successful pediatric MD, including 3D printing, advanced materials, drug delivery, and diagnostic imaging. To ensure the targeted development of MD for CYP, collaboration across multiple professional disciplines is required, facilitated by a platform to foster collaboration and drive innovation. The European Pediatric Translational Research Infrastructure (EPTRI) will be established as the European platform to support collaboration, including the life sciences industrial sector, to identify unmet needs in child health and support the development, adoption, and commercialization of pediatric MDs.

Directly Compressed Tablets: A Novel Drug-Containing Reservoir Combined with Hydrogel-Forming Microneedle Arrays for Transdermal Drug Delivery.

Microneedle (MN) patches consist of a hydrogel-forming MN array and a drug-containing reservoir. Drug-containing reservoirs documented in the literature include polymeric films and lyophilized wafers. While effective, both reservoir formulations are aqueous based, and so degradation can occur during formulation and drying for drugs inherently unstable in aqueous media. The preparation and characterization of novel, nonaqueous-based, directly compressed tablets (DCTs) for use in combination with hydrogel-forming MN arrays are described for the first time. In this work, a range of drug molecules are investigated. Precipitation of amoxicillin (AMX) and primaquine (PQ) in conventional hydrogel-forming MN arrays leads to use of poly(vinyl alcohol)-based MN arrays. Following in vitro permeation studies, in vivo pharmacokinetic studies are conducted in rats with MN patches containing AMX, levodopa/carbidopa (LD/CD), and levofloxacin (LVX). Therapeutically relevant concentrations of AMX (≥2 µg mL-1 ), LD (≥0.5 µg mL-1 ), and LVX (≥0.2 µg mL-1 ) are successfully achieved at 1, 2, and 1 h, respectively. Thus, the use of DCTs offers promise to expand the range of drug molecules that can be delivered transdermally using MN patches.

Development, Evaluation, and Pharmacokinetic Assessment of Polymeric Microarray Patches for Transdermal Delivery of Vancomycin Hydrochloride.

Methicillin-resistant Staphylococcus aureus (MRSA) can cause harmful and potentially deadly infections. Vancomycin remains the first-line antibiotic treatment for MRSA-derived infections. Nevertheless, as a peptide drug, it is poorly absorbed when administered orally because of its high molecular weight and low permeability in the gastrointestinal tract and is therefore administered intravenously for the treatment of systemic diseases. In order to circumvent some of the many drawbacks associated with intravenous injection, other routes of drug delivery should be investigated. One of the strategies which has been employed to enhance transdermal drug delivery is based on microarray patches (MAPs). This work, for the first time, describes successful transdermal delivery of vancomycin hydrochloride (VCL) using dissolving MAPs (DMAPs) and hydrogel-forming MAPs (HFMAPs). VCL was formulated into DMAPs and reservoirs [film dosage forms, lyophilized wafers, and compressed tablets (CSTs)] using excipients such as poly(vinyl pyrrolidone), poly(vinyl alcohol), sodium hyaluronate, d-sorbitol, and glycerol. In this study, HFMAPs were manufactured using aqueous blends containing poly(methylvinyl ether-co-maleic acid) cross-linked by esterification with poly(ethylene glycol). The VCL-loaded CSTs (60% w/w VCL) were the most promising reservoirs to be integrated with HFMAPs based on the physicochemical evaluations performed. Both HFMAPs and DMAPs successfully delivered VCL in ex vivo studies with the percentage of drug that permeated across the neonatal porcine skin recorded at 46.39 ± 8.04 and 7.99 ± 0.98%, respectively. In in vivo studies, the area under the plasma concentration time curve from time zero to infinity (AUC0-∞) values of 162.04 ± 61.84 and 61.01 ± 28.50 µg h/mL were achieved following the application of HFMAPs and DMAPs, respectively. In comparison, the AUC0-∞ of HFMAPs was significantly greater than that of the oral administration control group, which showed an AUC0-∞ of 30.50 ± 9.18 µg h/mL (p < 0.05). This work demonstrates that transdermal delivery of VCL is feasible using DMAPs and HFMAPs and could prove effective in the treatment of infectious diseases caused by MRSA, such as skin and soft tissue infections, lymphatic-related infections, and neonatal sepsis.

A sensitive HPLC-UV method for quantifying vancomycin in biological matrices: Application to pharmacokinetic and biodistribution studies in rat plasma, skin and lymph nodes.

Vancomycin (VCN) is an antibiotic used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-derived infections. As it has a relatively narrow therapeutic window, it is imperative to develop a sensitive and reliable analytical method for drug monitoring and pharmacokinetic purposes. In the present study, quick sample preparations and a sensitive high-performance liquid chromatography method using UV detection (HPLC-UV) have been developed and validated. The analytical method for detection and quantification of VCN in rat plasma, skin and lymph node samples was validated based on the Food and Drug Administration (FDA) and European Medicine Agency (EMEA) bioanalytical method validation guidelines. The optimised plasma sample preparation involved a simple protein precipitation step, with extraction recovery of 100.3 ±â€¯0.92 %. VCN in all biological matrices was analysed in a HPLC-UV system (215 nm) using a Cortecs® C18 column (4.6 × 150 mm, 2.7 µm particle size) fitted with a guard cartridge set at 20 °C. Reverse phase HPLC under gradient conditions, with mobile phase consisting of 20 mM phosphate buffer containing 0.5 % v/v of triethylamine and a mixture of methanol - acetonitrile (70:30, v/v), and runtime of 12 min/sample was employed. The calibration standards used for plasma ranged between 0.1-50 µg/ml, while in the skin and lymph node matrices, standards ranged between 0.05-50 µg/ml with correlation coefficients (R2) of ≥ 0.9995 for all matrices. The method was selective, sensitive, accurate and precise for detecting and quantifying VCN in the biological matrices used. The validated method was successfully utilised in the detection of VCN in a pharmacokinetic and organ biodistribution study carried out in rats following oral and IV bolus administration of the drug. This validated bioanalytical method offers a wide range of potential applications in clinical therapeutic drug monitoring, pharmacokinetics and toxicology.

Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery.

Treatment resistant depression is, by definition, difficult to treat using standard therapeutic interventions. Recently, esketamine has been shown as a viable rescue treatment option in patients in depressive crisis states. However, IV administration is associated with a number of drawbacks and advanced delivery platforms could provide an alternative parenteral route of esketamine dosing in patients. Hydrogel-forming microneedle arrays facilitate transdermal delivery of drugs by penetrating the outer layer of the skins surface, absorbing interstitial skin fluid and swelling. This subsequently facilitates permeation of medicines into the dermal microcirculation. This paper outlines the in vitro formulation development for hydrogel-forming microneedle arrays containing esketamine. Analytical methods for the detection and quantitation of esketamine were developed and validated according to International Conference on Harmonisation standards. Hydrogel-forming microneedle arrays were fully characterised for their mechanical strength and skin insertion properties. Furthermore, a series of esketamine containing polymeric films and lyophilised reservoirs were assessed as drug reservoir candidates. Dissolution testing and content drug recovery was carried out, followed by permeation studies using 350 µm thick neonatal porcine skin in modified Franz cell apparatus. Lead reservoir candidates were selected based on measured physicochemical properties and brought forward for testing in female Sprague-Dawley rats. Plasma samples were analysed using reverse phase high performance liquid chromatography for esketamine. Both polymeric film and lyophilised reservoirs candidate patches achieved esketamine plasma concentrations higher than the target concentration of 0.15-0.3 µg/ml over 24 h. Mean plasma concentrations in rats, 24 h post-application of microneedle patches with drug reservoir F3 and LW3, were 0.260 µg/ml and 0.498 µg/ml, respectively. This developmental study highlights the potential success of hydrogel-forming microneedle arrays as a transdermal drug delivery platform for ESK and supports moving to in vivo tests in a larger animal model.

Phytosomal nanocarriers as platforms for improved delivery of natural antioxidant and photoprotective compounds in propolis: An approach for enhanced both dissolution behaviour in biorelevant media and skin retention profiles.

Propolis has been reported to possess rich content of antioxidant compounds and may provide health benefits through oxidative stress reduction. Presently, the formulation activities used to enhance the drug delivery have been hampered due to inherently low aqueous solubility and poor transdermal permeation of the bioactive phenols and flavonoids. Here, we show, the formulation of propolis extract (PE) into phytosome delivery systems. The optimum antioxidant activity was attained through extraction process using 75% v/v ethanol. The phytosome was prepared using thin-layer hydration technique with l-α-Phosphatidylcholine as a phospholipid. Fourier transform infrared (FTIR) was used to investigate the occurrence of molecular interactions between formulation components. This innovative approach could encapsulate >40% of bioactive compounds in PE, namely caffeic acid, quercetin, and kaempferol. FTIR spectroscopy indicated new hydrogen bond formation, supporting successful phytosome formulation. The phytosomes enhanced the dissolution up to 4-folds of bioactive compounds in bio-mimicked release media, as well as improved penetrability and skin retention up to 6-folds of the three main compounds of propolis, when compared to non-encapsulated PE formulation. Importantly, the hydrogel containing phytosome showed a potential for UVA and UVB radiation absorption, indicated by the SPF values of higher than 15. To conclude, this work shows promising novel delivery approaches for PE in the treatment of organ injured stress oxidative and skin aging.

Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches.

Hydrogel-forming microneedle array patches (MAPs) have been proposed as viable clinical tools for patient monitoring purposes, providing an alternative to traditional methods of sample acquisition, such as venepuncture and intradermal sampling. They are also undergoing investigation in the management of non-melanoma skin cancers. In contrast to drug or vaccine delivery, when only a small number of MAP applications would be required, hydrogel MAPs utilised for sampling purposes or for tumour eradication would necessitate regular, repeat applications. Therefore, the current study was designed to address one of the key translational aspects of MAP development, namely patient safety. We demonstrate, for the first time in human volunteers, that repeat MAP application and wear does not lead to prolonged skin reactions or prolonged disruption of skin barrier function. Importantly, concentrations of specific systemic biomarkers of inflammation (C-reactive protein (CRP); tumour necrosis factor-α (TNF-α)); infection (interleukin-1ß (IL-1ß); allergy (immunoglobulin E (IgE)) and immunity (immunoglobulin G (IgG)) were all recorded over the course of this fixed study period. No biomarker concentrations above the normal, documented adult ranges were recorded over the course of the study, indicating that no systemic reactions had been initiated in volunteers. Building upon the results of this study, which serve to highlight the safety of our hydrogel MAP, we are actively working towards CE marking of our MAP technology as a medical device.

A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles.

Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.

Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules.

One specific technological advance in transdermal drug delivery is the development of dissolving microneedles (DMNs), which efficiently deliver therapeutics through a rapid dissolution of polymers after penetration into the skin. However, there is a limited range of water soluble, biodegradable polymers that can be used to manufacture DMN. Here, we report for the first time, the preparation and characterisation of a DMN system from the carbohydrate biopolymer, pullulan (PL). PL gels, of varying concentration, were studied for viscosity, film formation properties, and subsequently, microneedle formation. Model molecules and protein/peptide were loaded into PL DMN and characterised. The stability of model biomolecules, such as FITC-BSA and insulin, following DMN manufacture were assessed using circular dichroism. Ex-vivo porcine skin permeation studies using Franz diffusion cell apparatus for Flu-Na and FITC-BSA loaded PL-DMN were conducted. This study demonstrates that PL DMNs may serve as a promising tool for efficient transdermal drug delivery.

Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules.

The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P > 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% ± 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds.

Control of Klebsiella pneumoniae Infection in Mice by Using Dissolving Microarray Patches Containing Gentamicin.

Using a murine model of Klebsiella pneumoniae bacterial infection, we demonstrate that gentamicin dissolving microarray patches, applied to murine ears, could control K. pneumoniae infection. Mice treated with microarray patches had reduced bacterial burden in the nasal-associated lymphoid tissue and lungs compared with their untreated counterparts. This proof of concept study represents the first published data on the in vivo delivery of the antibiotic gentamicin via dissolving microarray patches, resulting in the control of bacterial infection.

Novel Hydrogel-Forming Microneedle Array for Intradermal Vaccination in Mice Using Ovalbumin as a Model Protein Antigen.

Global vaccination strategies have traditionally relied on the hypodermic needle and syringe model. However, to facilitate increased immunization coverage and reduce costs, novel methods of vaccine delivery are warranted. Dissolving microneedle arrays (MNs) have been proposed as an alternative approach to the hypodermic needle, offering the prospect for self-vaccination and increased immunogenicity via direct targeting of skin dendritic cells. This study, for the first time, compares the use of novel hydrogel-forming MNs and dissolving MNs for the delivery of a model protein antigen ovalbumin (OVA). We provide comparative data on both MN types in terms of in vitro characteristics and in vivo immunogenicity. Herein, both MN platforms were tested and characterized in terms of mechanical integrity and insertion properties using a validated skin insertion model. A comparative in vivo vaccination study in BALB/c mice was conducted, whereby anti-OVA specific IgG was used as a measure of delivery efficacy and subsequent immune response. While vaccination of mice with both MN platforms resulted in IgG responses, those vaccinated with dissolving MNs had significantly higher IgG titers ( p < 0.0149), despite the quantity of OVA delivered being significantly less. This study highlights the importance of MN design and the potential impact of dissolving MN polymers on the immune response to vaccine antigens. Furthermore, detailed studies are therefore required to elucidate the effects of polymer-vaccine interactions and their subsequent effect on immune responses.

Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride.

We investigated, for the first time, the potential for a hydrogel-forming microneedle (MN) patch to deliver the high-dose drug metformin HCl transdermally in a sustained manner. This may minimize some gastrointestinal side effects and small intestine absorption variations associated with oral delivery. Patches (two layers) were assembled from a lyophilised drug reservoir layer, with the MN layer made from aqueous blend of 20% w/w poly (methylvinylether-co-maleic acid) crosslinked by esterification with 7.5% w/w poly (ethylene glycol) 10,000 Da. >90% of metformin was recovered from homogeneous drug reservoirs. Drug reservoir dissolution time in PBS (pH 7.4) was <10 min. MN penetrated a validated skin model Parafilm® M consistently. Permeation of metformin HCl across dermatomed neonatal porcine skin in vitro was enhanced by using MN. The combined MN and metformin HCl reservoir patch (containing 75 mg or 50 mg metformin HCl, respectively) delivered 9.71 ±â€¯2.22 mg and 10.04 ±â€¯1.92 mg at 6 h, respectively, and 28.15 ±â€¯2.37 mg and 23.25 ±â€¯3.58 mg at 24 h, respectively.In comparison, 0.34 ±â€¯0.39 mg and 0.85 ±â€¯0.68 mg was delivered at 6 h, respectively, and 0.39 ±â€¯0.39 mg and 1.01 ±â€¯0.84 mg was delivered at 24 h, respectively, from a control set-up employing only the drug reservoirs. In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 ±â€¯0.51 µg/mL, increasing to 3.76 ±â€¯2.58 µg/ml at 3 h. A maximal concentration of 3.77 ±â€¯2.09 µg/ml was achieved at 24 h. Css was 3.2 µg/mL. Metformin transdermal bioavailability using MNs was estimated as 30%.Hydrogel-forming MN are a promising technology that has demonstrated successful transdermal delivery of metformin HCl. Potential clearly exists for administration of other high-dose drugs using this system.

Microneedle-Mediated Transdermal Delivery of Bevacizumab.

Bevacizumab is a recombinant humanized monoclonal antibody used clinically as a combination chemotherapeutic. Antibody therapeutics are usually formulated as parenteral injections, owing to their low oral bioavailability. Microneedle technology provides a transdermal alternative for drug-delivery using micron-scale needle structures to penetrate directly through the stratum corneum into the dermal interstitium. This study describes the design, formulation, and in vitro characterization of both dissolving and hydrogel-forming microneedle array platforms for transdermal delivery of bevacizumab. Bevacizumab recovery and transdermal permeation studies were conducted and analyzed using bevacizumab specific ELISA. Prototype microneedle-patches were tested in vivo in Sprague-Dawley rats with serum, exterior lumbar and axial lymph nodes, spleen, and skin tissue concentrations of bevacizumab reported. This work represents the first example of high dose transdermal delivery of an antibody therapeutic in vivo using dissolving and hydrogel-forming microneedle platforms. Basic pharmacokinetic parameters are described including hydrogel-forming microneedles: Cmax 358.2 ± 100.4 ng/mL, Tmax 48 h, AUC 44357 ± 4540, and Css 942 ± 95 ng/mL, highlighting the potential for these devices to provide sustained delivery of antibody therapeutics to the lymph and systemic circulation. Targeted delivery of chemotherapeutic agents to the lymphatic system by MN technology may provide new treatment options for cancer metastases.