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1.
Biomed J ; : 100750, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838984

ABSTRACT

BACKGROUND: Bone grafting is the standard treatment for critical bone defects, but autologous grafts have limitations like donor site morbidity and limited availability, while commercial artificial grafts may have poor integration with surrounding bone tissue, leading to delayed healing. Magnesium deficiency negatively impacts angiogenesis and bone repair. Therefore, incorporating magnesium into a synthetic biomaterial could provide an excellent bone substitute. This study aims to evaluate the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM), which could serve as an excellent bone substitute by incorporating magnesium. METHODS: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. RESULTS: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 minutes and a compressive strength of 4.39±0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. CONCLUSION: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

2.
Int J Nanomedicine ; 19: 2395-2407, 2024.
Article in English | MEDLINE | ID: mdl-38469059

ABSTRACT

Background: Recently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer. Methods: Astaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion. Results: In terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported. Conclusion: Our findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug.


Subject(s)
Antineoplastic Agents , Melanoma , Nanoparticles , Humans , Melanoma/drug therapy , Antineoplastic Agents/pharmacology , Cell Membrane , Xanthophylls
3.
Adv Healthc Mater ; 13(13): e2303867, 2024 05.
Article in English | MEDLINE | ID: mdl-38258406

ABSTRACT

Peripheral nerve regeneration and functional recovery rely on the chemical, physical, and structural properties of nerve guidance conduits (NGCs). However, the limited support for long-distance nerve regeneration and axonal guidance has hindered the widespread use of NGCs. This study introduces a novel nerve guidance conduit with oriented lateral walls, incorporating multi-walled carbon nanotubes (MWCNTs) within core-shell fibers prepared in a single step using a modified electrohydrodynamic (EHD) printing technique to promote peripheral nerve regeneration. The structured conduit demonstrated exceptional stability, mechanical properties, and biocompatibility, significantly enhancing the functionality of NGCs. In vitro cell studies revealed that RSC96 cells adhered and proliferated effectively along the oriented fibers, demonstrating a favorable response to the distinctive architectures and properties. Subsequently, a rat sciatic nerve injury model demonstrated effective efficacy in promoting peripheral nerve regeneration and functional recovery. Tissue analysis and functional testing highlighted the significant impact of MWCNT concentration in enhancing peripheral nerve regeneration and confirming well-matured aligned axonal growth, muscle recovery, and higher densities of myelinated axons. These findings demonstrate the potential of oriented lateral architectures with coaxial MWCNT fibers as a promising approach to support long-distance regeneration and encourage directional nerve growth for peripheral nerve repair in clinical applications.


Subject(s)
Nanotubes, Carbon , Nerve Regeneration , Peripheral Nerve Injuries , Rats, Sprague-Dawley , Sciatic Nerve , Animals , Nerve Regeneration/physiology , Nanotubes, Carbon/chemistry , Rats , Sciatic Nerve/physiology , Sciatic Nerve/injuries , Peripheral Nerve Injuries/therapy , Tissue Scaffolds/chemistry , Guided Tissue Regeneration/methods , Axons/physiology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
4.
Drug Discov Today ; 28(10): 103735, 2023 10.
Article in English | MEDLINE | ID: mdl-37573965

ABSTRACT

The blood-brain barrier (BBB) is a protective element of the neurovascular unit (NVU) surrounded by astrocytes, pericytes, extracellular matrix, and the tight junctional complex, which play a fundamental role in brain homeostasis. Due to its impeccable structural architecture, the BBB is referred to as the brain's gatekeeper, a near-impenetrable barrier to therapeutics. This review summarises the significant strides that have been made in the last 5 years towards circumventing the BBB and developing efficient drug delivery systems. Challenges associated with several CNS disorders related to BBB failure and exploitation of this unique NVU component for targeted treatment of brain-related disorders are also discussed.


Subject(s)
Blood-Brain Barrier , Brain Diseases , Humans , Brain , Astrocytes , Biological Transport
5.
Drug Deliv Transl Res ; 13(3): 852-861, 2023 03.
Article in English | MEDLINE | ID: mdl-36253518

ABSTRACT

This study is aimed to fabricate tetanus toxoid laden microneedle patches by using a polymeric blend comprising of polyvinyl pyrrolidone and sodium carboxymethyl cellulose as base materials and sorbitol as a plasticizer. The tetanus toxoid was mixed with polymeric blend and patches were prepared by using vacuum micromolding technique. Microneedle patches were evaluated for physical attributes such as uniformity of thickness, folding endurance, and swelling profile. Morphological features were assessed by optical and scanning electron microscopy. In vitro performance of fabricated patches was studied by using bicinchoninic acid assay (BCA). Insertion ability of microstructures was studied in vitro on model skin parafilm and in vivo in albino rat. In vivo immunogenic activity of the formulation was assessed by recording immunoglobulin G (IgG) levels, interferon gamma (IFN-γ) levels, and T-cell (CD4+ and CD8+) count following the application of dosage forms. Prepared patches, displaying sharp-tipped and smooth-surfaced microstructures, remained intact after 350 ± 36 foldings. Optimized microneedle patch formulation showed ~ 74% swelling and ~ 85.6% vaccine release within an hour. The microneedles successfully pierced parafilm. Histological examination of microneedle-treated rat skin confirmed disruption of epidermis without damaging the underneath vasculature. A significant increase in IgG levels (~ 21%), IFN-γ levels (~ 30%), CD4+ (~ 41.5%), and CD8+ (~ 48.5%) cell count was observed in tetanus vaccine-loaded microneedle patches treated albino rats with respect to control (untreated) group at 42nd day of immunization. In conclusion, tetanus toxoid-loaded microneedle patches can be considered as an efficient choice for transdermal delivery of vaccine without inducing pain commonly experienced with hypodermic needles.


Subject(s)
Paraffin , Tetanus Toxoid , Administration, Cutaneous , Drug Delivery Systems/methods , Immunoglobulin G , Needles , Polymers/chemistry , Transdermal Patch , Animals , Rats
6.
Micromachines (Basel) ; 13(10)2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36296147

ABSTRACT

Personalised drug delivery systems with the ability to offer real-time imaging and control release are an advancement in diagnostic and therapeutic applications. This allows for a tailored drug dosage specific to the patient with a release profile that offers the optimum therapeutic effect. Coupling this application with medical imaging capabilities, real-time contrast can be viewed to display the interaction with the host. Current approaches towards such novelty produce a drug burst release profile and contrasting agents associated with side effects as a result of poor encapsulation of these components. In this study, a 3D-printed drug delivery matrix with real-time imaging is engineered. Polycaprolactone (PCL) forms the bulk structure and encapsulates tetracycline hydrochloride (TH), an antibiotic drug and Iron Oxide Nanoparticles (IONP, Fe3O4), a superparamagnetic contrasting agent. Hot melt extrusion (HME) coupled with fused deposition modelling (FDM) is utilised to promote the encapsulation of TH and IONP. The effect of additives on the formation of micropores (10-20 µm) on the 3D-printed surface was investigated. The high-resolution process demonstrated successful encapsulation of both bioactive and nano components to present promising applications in drug delivery systems, medical imaging and targeted therapy.

7.
Nanomaterials (Basel) ; 12(12)2022 Jun 11.
Article in English | MEDLINE | ID: mdl-35745355

ABSTRACT

Mesoporous Silica Nanoparticles (MSNs) have received increasing attention in biomedical applications due to their tuneable pore size, surface area, size, surface chemistry, and thermal stability. The biocompatibility of MSNs, although generally believed to be satisfactory, is unclear. Physicochemical properties of MSNs, such as diameter size, morphology, and surface charge, control their biological interactions and toxicity. Experimental conditions also play an essential role in influencing toxicological results. Therefore, the present study includes studies from the last five years to statistically analyse the effect of various physicochemical features on MSN-induced in-vitro cytotoxicity profiles. Due to non-normally distributed data and the presence of outliers, a Kruskal-Wallis H test was conducted on different physicochemical characteristics, including diameter sizes, zeta-potential measurements, and functionalisation of MSNs, based on the viability results, and statistical differences were obtained. Subsequently, pairwise comparisons were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. Other experimental parameters, such as type of cell line used, cell viability measurement assay, and incubation time, were also explored and analysed for statistically significant results.

8.
Micromachines (Basel) ; 13(4)2022 Apr 18.
Article in English | MEDLINE | ID: mdl-35457946

ABSTRACT

Three dimensional printing (3DP), or additive manufacturing, is an exponentially growing process in the fabrication of various technologies with applications in sectors such as electronics, biomedical, pharmaceutical and tissue engineering. Micro and nano scale printing is encouraging the innovation of the aforementioned sectors, due to the ability to control design, material and chemical properties at a highly precise level, which is advantageous in creating a high surface area to volume ratio and altering the overall products' mechanical and physical properties. In this review, micro/-nano printing technology, mainly related to lithography, inkjet and electrohydrodynamic (EHD) printing and their biomedical and electronic applications will be discussed. The current limitations to micro/-nano printing methods will be examined, covering the difficulty in achieving controlled structures at the miniscule micro and nano scale required for specific applications.

9.
Int J Pharm ; 616: 121512, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35085730

ABSTRACT

The study aimed to fabricate naproxen sodium loaded in-situ gels of sodium alginate. Different in-situ gel forming solutions of naproxen sodium and sodium alginate were prepared and gel formation was studied in different physiological ions i.e., CaCl2 and Ca-gluconate. The prepared gel formulations were evaluated for different physical attributes such as gelation time, sol-gel fraction, ATR-FTIR spectroscopy and in silico molecular dynamics (MD) simulations. Drug release studies were carried out in a dialysis membrane using USP dissolution basket apparatus-I. In vivo anti-inflammatory studies were performed in Sprague-Dawley rats having carrageenan-induced hind paw inflammation. Higher polymer concentration in formulations resulted in decreased gelation time and an increased gel fraction. The ATR-FTIR and MD simulation revealed H-bonding between the alginate and naproxen sodium at 3500-3200 cm-1 with a RMSD of ∼2.8 Å and binding free energy ΔGpred (GB) = -10.93 kcal/mol. In vitro drug release studies from F8CAG suggested a sustained release of naproxen sodium. In vivo studies revealed a continuous decrease in swelling degree (≈-5.28 ± 0.210 mm) in inflamed hind paw of Sprague-Dawley rats over 96 h. The in-situ gel forming injectable preparation (F8CAG) offers a sustained release of naproxen sodium in the articular cavity which promises the treatment of chronic inflammatory conditions such as arthritis.


Subject(s)
Naproxen , Renal Dialysis , Animals , Delayed-Action Preparations , Gels/chemistry , Naproxen/chemistry , Rats , Rats, Sprague-Dawley
10.
BMC Res Notes ; 14(1): 469, 2021 Dec 24.
Article in English | MEDLINE | ID: mdl-34952633

ABSTRACT

OBJECTIVE: The use of benchtop metabolic profiling technology based on nuclear magnetic resonance (NMR) was evaluated in a small cohort of cats with a view to applying this as a viable and rapid metabolic tool to support clinical decision making. RESULTS: Urinary metabolites were analysed from four subjects consisting of two healthy controls and two chronic kidney disease (CKD) IRIS stage 2 cases. The study identified 15 metabolites in cats with CKD that were different from the controls. Among them were acetate, creatinine, citrate, taurine, glycine, serine and threonine. Benchtop NMR technology is capable of distinguishing between chronic kidney disease case and control samples in a pilot feline cohort based on metabolic profile. We offer perspectives on the further development of this pilot work and the potential of the technology, when combined with sample databases and computational intelligence techniques to offer a clinical decision support tool not only for cases of renal disease but other metabolic conditions in the future.


Subject(s)
Metabolomics , Renal Insufficiency, Chronic , Animals , Cats , Creatinine , Magnetic Resonance Spectroscopy , Metabolome
11.
Mol Cell Biochem ; 476(11): 4133-4137, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34312783

ABSTRACT

Chronic kidney disease (CKD) is a renal dysfunction that can lead to high rates of mortality and morbidity, particularly when coupled with late diagnosis. CKD has become a major health problem due to its challenging detection at early stages when clear symptoms are yet to be presented. Thus, CKD is likely to be identified when the substantive conditions of the disease are manifest. In order to address the development of the disease and provide necessary treatments at the initial stage, the investigation of new biomarkers and metabolites associated with early detection of CKD are needed. Identified metabolites could be used to confirm the presence of the disease, obtain information on its mechanism and facilitate the development of novel pharmaceutical treatments. Such metabolites may be detected from biofluids and tissues using a range of analytical techniques. There are a number of metabolites that have been identified by mass spectrometry at high sensitivities, whilst the detection of metabolites directly from biofluids using NMR could present a more rapid way to expand our understanding of this disease. This review is focused on NMR-based metabolomics associated with CKD in humans and animals.


Subject(s)
One Health , Renal Insufficiency, Chronic/diagnosis , Animals , Biomarkers/analysis , Early Diagnosis , Humans , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Metabolomics/methods , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/therapy
12.
Adv Drug Deliv Rev ; 178: 113840, 2021 11.
Article in English | MEDLINE | ID: mdl-34147533

ABSTRACT

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight about the advances in tablet excipients, manufacturing, analytical techniques and deployment of Quality by Design (QbD). Various excipients offering novel functionalities such as solubility enhancement, super-disintegration, taste masking and drug release modifications have been developed. Furthermore, co-processed multifunctional ready-to-use excipients, particularly for tablet dosage forms, have benefitted manufacturing with shorter processing times. Advances in granulation methods, including moist, thermal adhesion, steam, melt, freeze, foam, reverse wet and pneumatic dry granulation, have been proposed to improve product and process performance. Furthermore, methods for particle engineering including hot melt extrusion, extrusion-spheronization, injection molding, spray drying / congealing, co-precipitation and nanotechnology-based approaches have been employed to produce robust tablet formulations. A wide range of tableting technologies including rapidly disintegrating, matrix, tablet-in-tablet, tablet-in-capsule, multilayer tablets and multiparticulate systems have been developed to achieve customized formulation performance. In addition to conventional invasive characterization methods, novel techniques based on laser, tomography, fluorescence, spectroscopy and acoustic approaches have been developed to assess the physical-mechanical attributes of tablet formulations in a non- or minimally invasive manner. Conventional UV-Visible spectroscopy method has been improved (e.g. fiber-optic probes and UV imaging-based approaches) to efficiently record the dissolution profile of tablet formulations. Numerous modifications in tableting presses have also been made to aid machine product changeover, cleaning, and enhance efficiency and productivity. Various process analytical technologies have been employed to track the formulation properties and critical process parameters. These advances will contribute to a strategy for robust tablet dosage forms with excellent performance attributes.


Subject(s)
Pharmaceutical Preparations/chemistry , Technology, Pharmaceutical , Administration, Oral , Drug Compounding , Humans , Pharmaceutical Preparations/administration & dosage
13.
Adv Drug Deliv Rev ; 175: 113823, 2021 08.
Article in English | MEDLINE | ID: mdl-34089777

ABSTRACT

Advancements in technology and material development in recent years has led to significant breakthroughs in the remit of fiber engineering. Conventional methods such as wet spinning, melt spinning, phase separation and template synthesis have been reported to develop fibrous structures for an array of applications. However, these methods have limitations with respect to processing conditions (e.g. high processing temperatures, shear stresses) and production (e.g. non-continuous fibers). The materials that can be processed using these methods are also limited, deterring their use in practical applications. Producing fibrous structures on a nanometer scale, in sync with the advancements in nanotechnology is another challenge met by these conventional methods. In this review we aim to present a brief overview of conventional methods of fiber fabrication and focus on the emerging fiber engineering techniques namely electrospinning, centrifugal spinning and pressurised gyration. This review will discuss the fundamental principles and factors governing each fabrication method and converge on the applications of the resulting spun fibers; specifically, in the drug delivery remit and in regenerative medicine.


Subject(s)
Biomedical Engineering/methods , Drug Delivery Systems/methods , Materials Science/methods , Precision Medicine/methods , Regenerative Medicine/methods , Centrifugation , Electromagnetic Phenomena , Humans , Pressure
14.
Adv Drug Deliv Rev ; 176: 113788, 2021 09.
Article in English | MEDLINE | ID: mdl-33957180

ABSTRACT

Electrohydrodynamic atomisation (EHDA) technologies have evolved significantly over the past decade; branching into several established and emerging healthcare remits through timely advances in the engineering sciences and tailored conceptual process designs. More specifically for pharmaceutical and drug delivery spheres, electrospraying (ES) has presented itself as a high value technique enabling a plethora of different particulate structures. However, when coupled with novel formulations (e.g. co-flows) and innovative device aspects (e.g., materials and dimensions), core characteristics of particulates are manipulated and engineered specifically to deliver an application driven need, which is currently lacking, ranging from imaging and targeted delivery to controlled release and sensing. This demonstrates the holistic nature of these emerging technologies; which is often overlooked. Parametric driven control during particle engineering via the ES method yields opportunistic properties when compared to conventional methods, albeit at ambient conditions (e.g., temperature and pressure), making this extremely valuable for sensitive biologics and molecules of interest. Furthermore, several processing (e.g., flow rate, applied voltage and working distance) and solution (e.g., polymer concentration, electrical conductivity and surface tension) parameters impact ES modes and greatly influence the production of resulting particles. The formation of a steady cone-jet and subsequent atomisation during ES fabricates particles demonstrating monodispersity (or near monodispersed), narrow particle size distributions and smooth or textured morphologies; all of which are successfully incorporated in a one-step process. By following a controlled ES regime, tailored particles with various intricate structures (hollow microspheres, nanocups, Janus and cell-mimicking nanoparticles) can also be engineered through process head modifications central to the ES technique (single-needle spraying, coaxial, multi-needle and needleless approaches). Thus, intricate formulation design, set-up and combinatorial engineering of the EHDA process delivers particulate structures with a multitude of applications in tissue engineering, theranostics, bioresponsive systems as well as drug dosage forms for specific delivery to diseased or target tissues. This advanced technology has great potential to be implemented commercially, particularly on the industrial scale for several unmet pharmaceutical and medical challenges and needs. This review focuses on key seminal developments, ending with future perspectives addressing obstacles that need to be addressed for future advancement.


Subject(s)
Drug Delivery Systems , Drug Design , Technology, Pharmaceutical/methods , Animals , Electric Conductivity , Electrochemistry , Humans , Hydrodynamics , Particle Size , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry , Polymers/chemistry
15.
Pharm Res ; 38(1): 165-177, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33534130

ABSTRACT

AIM: The aim of this study was to fabricate polymeric microneedles, loaded with macrolides (erythromycin, azithromycin), using hyaluronic acid and polyvinyl pyrollidone. METHODS: These microneedles were fabricated using a vacuum micromolding technique. The integrity of the microneedle patches was studied by recording their morphologic features, folding endurance, swelling and micro-piercing. Physicochemical characteristics were studied by differential scanning calorimetry, thermogravimetric analysis and fourier transform infrared spectroscopy. In-vitro drug release, antibiofilm and effect of microneedle patch on wound healing were also studied to confirm the efficacy of the formulations. RESULTS: Formulated patches displayed acceptable folding endurance (>100) and uniform distribution of microneedles (10 × 10) that can penetrate parafilm. Differential scanning calorimetry results depict a decrease in the crystallinity of macrolides following their incorporation in to a polymer matrix. Percentage release of azithromycin and erythromycin from the polymeric patch formulations (over 30 min) was 90% and 63% respectively. Broadly, the zone of bacterial growth inhibition follows the same order for Staphylococcus aureus, Escherichia coli and Salmonella enterica. After 5 days of treatment with azithromycin patches, the wound healing was complete and skin structure (e.g. hair follicles and dermis) was regenerated. CONCLUSION: It was concluded that azithromycin loaded microneedle patches can be used to treat biofilms in the infected wounds.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Biofilms/drug effects , Drug Delivery Systems/methods , Wound Healing/drug effects , Wound Infection/drug therapy , Administration, Cutaneous , Animals , Anti-Bacterial Agents/pharmacokinetics , Azithromycin/administration & dosage , Azithromycin/pharmacokinetics , Disease Models, Animal , Drug Liberation , Erythromycin/administration & dosage , Erythromycin/pharmacokinetics , Escherichia coli/drug effects , Humans , Male , Microbial Sensitivity Tests , Rats , Salmonella enterica/drug effects , Skin/injuries , Skin/metabolism , Skin/microbiology , Staphylococcus aureus/drug effects , Transdermal Patch , Wound Infection/microbiology
16.
AAPS PharmSciTech ; 22(1): 23, 2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33400042

ABSTRACT

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.


Subject(s)
Cannabidiol/administration & dosage , Cannabinoids/administration & dosage , Nanofibers/chemistry , Administration, Oral , Cannabidiol/chemistry , Cannabinoids/chemistry , Drug Compounding , Drug Liberation , Polymethacrylic Acids/chemistry , Povidone/chemistry
17.
J Drug Target ; 29(1): 60-68, 2021 01.
Article in English | MEDLINE | ID: mdl-32649227

ABSTRACT

The aim of this study was to develop heparin sodium loaded microneedle patches using different compositions of polyvinyl alcohol polymer and sorbitol. A vacuum micromolding technique was used to fabricate microneedle patches while heparin sodium was loaded into needle tips. Physical features of patches were evaluated by measuring thickness, width, folding endurance and swelling percentage. Patches were also characterised by optical microscopy and scanning electron microscopy to determine the microneedle length and surface morphologies. A preliminary assessment of the microneedle performance was studied by examining the in-vitro insertion to the parafilm and recording the in-vitro drug release profile. In-vivo activity of patches was confirmed by measuring activated partial thromboplastin time and histological examination of the micropierced skin tissues. Prepared patches were clear, smooth; uniform in appearance; with sharp pointed microprojections and remained intact after 1000 folding. The microneedles were stiffer in nature, as they reproduce microcavities in the parafilm membrane following hand pushing without any structural loss. Insertion study results showed successful insertion of microneedles into the parafilm. Disrupted stratum corneum evident from histological examination confirmed successful insertion of the microneedle without affecting the vasculature. In-vitro release study confirmed ∼92% release of the loaded drug within 120 min. A significant prolongation of activated partial thromboplastin time (4 folds as compared to negative control) was recorded following the application of heparin sodium loaded microneedle patch onto rabbit skin. In conclusion microneedles are a valuable drug delivery system, benefiting the patients with minimal skin invasion and also allowing self-administration of heparin sodium in a sustained release manner for the management of chronic ailments.


Subject(s)
Anticoagulants/administration & dosage , Heparin/administration & dosage , Microinjections/methods , Needles , Skin/drug effects , Transdermal Patch , Administration, Cutaneous , Animals , Female , Heparin/metabolism , Male , Microinjections/instrumentation , Rabbits , Skin/metabolism
18.
Pharmaceutics ; 12(10)2020 Oct 03.
Article in English | MEDLINE | ID: mdl-33023033

ABSTRACT

SARS-CoV-2 has affected people from all age groups, races and ethnicities. Given that many infected individuals are asymptomatic, they transmit the disease to others unknowingly, which has resulted in the spread of infection at an alarming rate. This review aims to provide an overview of the pathophysiology, preventive measures to reduce the disease spread, therapies currently in use, an update on vaccine development and opportunities for vaccine delivery. The World Health Organization has advised several precautions including social distancing, hand washing and the use of PPE including gloves and face masks for minimizing the spread of SARS-CoV-2 infection. At present, several antiviral therapies previously approved for other infections are being repositioned to study their efficacy against SARS-CoV-2. In addition, some medicines (i.e., remdesivir, chloroquine, hydroxychloroquine) have received emergency use authorisation from the FDA. Plasma therapy has also been authorised for emergency use for the treatment of COVID-19 on a smaller scale. However, no vaccine has been approved so far against this virus. Nevertheless, several potential vaccine targets have been reported, and development of different types of vaccines including DNA, mRNA, viral vector, inactivated, subunit and vaccine-like particles is in process. It is concluded that a suitable candidate delivered through an advanced drug delivery approach would effectively boost the immune system against this coronavirus.

19.
Eur J Pharm Biopharm ; 156: 20-39, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32871196

ABSTRACT

The research presented here shows QbD implementation for the optimisation of the key process parameters in electrohydrodynamic atomisation (EHDA). Here, the electrosprayed nanoparticles and electrospun fibers consisting of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial DOE was used to assess the various parameters (applied voltage, deposition distance, flow rate). Further particle and fiber analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), particle/fiber size distribution. In addition to this in vitro release studied were carried out using fluorescein and Rhodamine B as model dyes and in vitro permeation studies were applied. The results show a significant difference in the morphology of resultant structures as well as a more rapid release profile for the PVP particles and fibers in comparison to the sustained release profiles found with PCL. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and showed 100% drug release within 120 min for PVP particles. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the electrospun MN coating released a large amount of the loaded drug within 6 h. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range drugs within a polymeric matrix giving rise to the potential of developed personalised medical devices.


Subject(s)
Microinjections/instrumentation , Needles , Polymers/chemistry , Qualitative Research , Technology, Pharmaceutical/instrumentation , Drug Liberation , Microinjections/standards , Needles/standards , Polyesters/chemistry , Polyesters/standards , Polymers/standards , Povidone/chemistry , Povidone/standards , Spectroscopy, Fourier Transform Infrared/methods , Technology, Pharmaceutical/standards
20.
BMC Res Notes ; 13(1): 333, 2020 Jul 11.
Article in English | MEDLINE | ID: mdl-32653027

ABSTRACT

OBJECTIVE: Cyanide is a highly toxic compound, and the consumption of products containing cyanide is a significant public health concern. Conversely, ß-carotene possesses essential nutritional attributes for human health, therefore the characterisation and quantification of both compounds in food products is fundamental. Herein, cyanide and ß-carotene levels in two flours produced from the roots of two varieties of cassava (Manihot esculenta crantz), namely UMUCASS-38(TMS 01/1371) and NR-8082, and their associated food products were detected and quantified. RESULTS: The cyanide content of NR-8082 and UMUCASS-38 flours was determined at 18.01 ± 0.01 ppm and 17.02 ± 0.02 ppm (mean ± SD), respectively. These flours contained significantly higher (p < 0.05) than the residual cyanide levels determined in the cookies and cake produced therefrom with levels of 10.00 ± 0.00 ppm and 7.10 ± 0.14 ppm (mean ± SD), respectively. The levels of ß-carotene determined in both the cake and cookie samples varied significantly (p < 0.05). The highest levels of ß-carotene at 6.53 ± 0.02 µg/g (mean ± SD) were determined in raw roots of UMUCASS-38. While NR-8082 levels of ß-carotene were less than UMUCASS-38 at 1.12 ± 0.02 µg/g (mean ± SD). Processing the roots into flour reduced the ß-carotene content to 4.78 ± 0.01 µg/g and 0.76 ± 0.02 µg/g (mean ± SD) in UMUCASS-38 and NR-8082 flours, respectively. Cookies and cake produced from flour derived from the UMUCASS-38 variety had (mean ± SD) 2.15 ± 0.01 µg/g and 2.84 ± 0.04 µg/g of ß-carotene, respectively.


Subject(s)
Cyanides/analysis , Flour/analysis , Manihot/chemistry , beta Carotene/analysis , Glycosides/analysis , Plant Roots/chemistry
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