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1.
Discov Nano ; 19(1): 145, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39256285

ABSTRACT

Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs' ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable "theranostic alternatives" for breast cancer treatment.

2.
Int J Biol Macromol ; 277(Pt 1): 133984, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39053830

ABSTRACT

Small interfering RNA (siRNA) holds promise as a therapeutic approach for various diseases, yet challenges persist in achieving efficient delivery, biodistribution, and minimizing off-target effects. Lipidic nanoformulations are being developed to address these hurdles, but the optimal dose for preclinical investigations remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of nanoformulated siRNA and explore factors influencing dose and biodistribution, informing future research in this field. A comprehensive search across four electronic databases identified 25 potential studies, with 15 selected for meta-analysis after screening. Quality assessment was conducted using SYRCLE's risk of bias tool modified for animal studies based on research question. Study found an average siRNA dose of 1.513 ± 0.377 mg/kg with mean downregulation of 65.79 % achieved, with siRNA-LNPs mainly accumulating in the liver. While individual factors showed no significant correlation, a positive association between dose and downregulation was observed, alongside other influencing factors. Extrapolating intravenous doses to potential oral doses, we suggest an initial oral dose range of 1.5 to 8 mg/kg, considering siRNA-LNPs bioavailability. These findings contribute to advancing RNA interference research and encourage further exploration of siRNA-based treatments in personalized medicine.


Subject(s)
Lipids , Nanoparticles , RNA, Small Interfering , RNA, Small Interfering/genetics , RNA, Small Interfering/administration & dosage , Nanoparticles/chemistry , Humans , Animals , Lipids/chemistry , Down-Regulation/drug effects , Tissue Distribution , RNA Interference , Liposomes
3.
J Mater Chem B ; 12(33): 7977-8006, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-38946466

ABSTRACT

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.


Subject(s)
Bandages , Wound Healing , Humans , Wound Healing/drug effects , Animals , Biocompatible Materials/chemistry
4.
Mol Biol Rep ; 51(1): 746, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874663

ABSTRACT

BACKGROUND: Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic pathologies. We pioneered the surgical use of hAM to treat retinal pathologies such as macular holes, tears, and retinal detachments, and to overcome photoreceptor damage in age-related macular degeneration. Although hAM contributed to improved outcomes, the mechanisms of its effects are not yet fully understood. The characterization and explanation of the effects of hAM would allow the adoption of this new natural product in different retinal pathologies, operative contexts, and hAM formulations. At this end, we studied the properties of a hAM extract (hAME) on the ARPE-19 cells. METHODS AND RESULTS: A non-denaturing sonication-based technique was developed to obtain a suitable hAME. Viability, proliferation, apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) were studied in hAME-treated ARPE-19 cells. The hAME was able to increase ARPE-19 cell viability even in the presence of oxidative stress (H2O2, TBHP). Moreover, hAME prevented the expression of EMT features, such as EMT-related proteins, fibrotic foci formation, and migration induced by different cytokines. CONCLUSIONS: Our results demonstrate that the hAME retains most of the properties observed in the whole tissue by others. The hAME, other than providing a manageable research tool, could represent a cost-effective and abundant drug to treat retinal pathologies in the future.


Subject(s)
Amnion , Apoptosis , Cell Proliferation , Cell Survival , Oxidative Stress , Retinal Pigment Epithelium , Humans , Amnion/cytology , Amnion/drug effects , Cell Line , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/cytology , Cell Survival/drug effects , Apoptosis/drug effects , Oxidative Stress/drug effects , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Tissue Extracts/pharmacology
5.
J Control Release ; 371: 67-84, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38768662

ABSTRACT

In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes.


Subject(s)
Administration, Ophthalmic , Drug Delivery Systems , Gels , Humans , Animals , Biological Availability , Eye/metabolism , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry , Ophthalmic Solutions/administration & dosage
6.
Chem Biol Interact ; 395: 111009, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38641145

ABSTRACT

The escalating prevalence of lung diseases underscores the need for innovative therapies. Dysbiosis in human body microbiome has emerged as a significant factor in these diseases, indicating a potential role for synbiotics in restoring microbial equilibrium. However, effective delivery of synbiotics to the target site remains challenging. Here, we aim to explore suitable nanoparticles for encapsulating synbiotics tailored for applications in lung diseases. Nanoencapsulation has emerged as a prominent strategy to address the delivery challenges of synbiotics in this context. Through a comprehensive review, we assess the potential of nanoparticles in facilitating synbiotic delivery and their structural adaptability for this purpose. Our review reveals that nanoparticles such as nanocellulose, starch, and chitosan exhibit high potential for synbiotic encapsulation. These offer flexibility in structure design and synthesis, making them promising candidates for addressing delivery challenges in lung diseases. Furthermore, our analysis highlights that synbiotics, when compared to probiotics alone, demonstrate superior anti-inflammatory, antioxidant, antibacterial and anticancer activities. This review underscores the promising role of nanoparticle-encapsulated synbiotics as a targeted and effective therapeutic approach for lung diseases, contributing valuable insights into the potential of nanomedicine in revolutionizing treatment strategies for respiratory conditions, ultimately paving the way for future advancements in this field.


Subject(s)
Lung Diseases , Synbiotics , Humans , Lung Diseases/drug therapy , Nanostructures/chemistry , Lung/drug effects , Lung/pathology , Animals , Nanoparticles/chemistry
7.
Int J Pharm ; 654: 123974, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38447777

ABSTRACT

Sesamol, a lignan, obtained from sesame seeds (Sesamum indicum Linn., Pedaliaciae) has a promising antioxidant, and anti-inflammatory profile. When applied topically, free sesamol rapidly crosses skin layers and gets absorbed in systemic circulation. Its encapsulation into solid lipid nanoparticles not only improved its localised delivery to skin but also resulted in better skin retention, as found in ex-vivo skin retention studies. Free and encapsulated sesamol was compared for antimicrobial and antibiofilm activity against some common skin pathogens and it was found that encapsulation improved the antimicrobial profile by 200%. In vivo evaluation in diabetic open excision wound model suggested that encapsulation of sesamol in SLNs substantially enhanced its wound healing potential when investigated for biophysical, biochemical and histological parameters. It was envisaged that this was achieved via inhibiting bacterial growth and clearing the bacterial biofilm at the wound site, and by regulating oxidative stress in skin tissue.


Subject(s)
Anti-Infective Agents , Liposomes , Nanoparticles , Phenols , Benzodioxoles/pharmacology , Wound Healing
8.
Chem Phys Lipids ; 259: 105374, 2024 03.
Article in English | MEDLINE | ID: mdl-38176612

ABSTRACT

Soluble alpha-amylases play an important role in the catabolism of polysaccharides. In this work, we show that the malt α -amylase can interact with the lipid membrane and further alter its mechanical properties. Vesicle fluctuation spectroscopy is used for quantitative measurement of the membrane bending rigidity of phosphatidylcholines lipid vesicles from the shape fluctuation based on the whole contour of Giant Unilamellar Vesicles (GUVs). The bending rigidity of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid vesicles in water increases significantly with the presence of 0.14 micromolar alpha-amylase (AA) in the exterior solution. It appears that the enzyme present in the external solution interacts with the outer layer of the bilayer membrane, leading to an asymmetry of the solution on either side of the bilayer membrane and altering its elasticity. At AA concentration of 1.5 micromolars and above, changes in the morphology of the GUV membrane are observed. The interaction between AA in the external solution and the external leaflet causes the bilayer membrane to curve spontaneously, leading to the formation of outbuds, giving a positive spontaneous curvature of C0 ≤ 0.05 µm-1 at ≈ 1 mg / ml of the AA concentration. We validate and characterize its concentration-dependent role in stabilizing the membrane curvature. Our findings indicate that the involvement of the enzyme, depending on the concentration, can have a considerable effect on the mechanical characteristics of the membrane.


Subject(s)
Lipid Bilayers , alpha-Amylases , Lipid Bilayers/chemistry , Phosphatidylcholines/chemistry , Unilamellar Liposomes/chemistry
9.
J Funct Biomater ; 14(8)2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37623663

ABSTRACT

Drug-delivery systems employing phytopharmaceuticals based on the leads in traditional knowledge offers not only an alternative but quicker and more economic strategy for drug development. Nanophytopharmaceuticals promise remarkable opportunities with the ability to overcome challenges associated with herbal medicines, such as low solubility and bioavailability, poor target specificity, and shelf life. Berberis extracts documented as Ropana (wound healer) in Sushruta Samhita are a popular traditional remedy that is amiss in the modern system of medicine as it exhibits very poor biopharmaceutical properties. Poor solubility and bioavailability necessitate the administration of high doses to achieve the desired therapeutic effects. Exploiting the diversified type of compounds with pleiotropic properties present in Berberis, the biopharmaceutical properties were engineered using an optimized freeze-dried extract and developed solid lipid nanoparticles (SLNs) as an effective drug-delivery system. An industrially viable and environment-friendly hot high-pressure homogenization technique led to a stable formulation with an average particle size of 178.4 nm, as well as a 7-fold increase in loading and a significant entrapment of 91 ± 1.25%. The pharmacodynamic studies of developed nanosystems in excision-wound models showed faster and complete healing of wounds with no scars.

10.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 28.
Article in English | MEDLINE | ID: mdl-37259345

ABSTRACT

Polycystic Ovarian Syndrome (PCOS) comprises a set of symptoms that pose significant risk factors for various diseases, including type 2 diabetes, cardiovascular disease, and cancer. Effective and safe methods to treat all the pathological symptoms of PCOS are not available. The gut microbiota has been shown to play an essential role in PCOS incidence and progression. Many dietary plants, prebiotics, and probiotics have been reported to ameliorate PCOS. Gut microbiota shows its effects in PCOS via a number of mechanistic pathways including maintenance of homeostasis, regulation of lipid and blood glucose levels. The effect of gut microbiota on PCOS has been widely reported in animal models but there are only a few reports of human studies. Increasing the diversity of gut microbiota, and up-regulating PCOS ameliorating gut microbiota are some of the ways through which prebiotics, probiotics, and polyphenols work. We present a comprehensive review on polyphenols from natural origin, probiotics, and fecal microbiota therapy that may be used to treat PCOS by modifying the gut microbiota.

11.
Gels ; 9(3)2023 Mar 19.
Article in English | MEDLINE | ID: mdl-36975693

ABSTRACT

The current study describes a suppository base composed of aqueous gelatin solution emulsifying oil globules with probiotic cells dispersed within. The favorable mechanical properties of gelatin to provide a solid gelled structure, and the tendency of its proteins to unravel into long strings that interlace when cooled, lead to a three-dimensional structure that can trap a lot of liquid, which was exploited herein to result in a promising suppository form. The latter maintained incorporated probiotic spores of Bacillus coagulans Unique IS-2 in a viable but non-germinating form, preventing spoilage during storage and imparting protection against the growth of any other contaminating organism (self-preserved formulation). The gelatin-oil-probiotic suppository showed uniformity in weight and probiotic content (23 ± 2.481 × 108 cfu) with favorable swelling (double) followed by erosion and complete dissolution within 6 h of administration, leading to the release of probiotic (within 45 min) from the matrix into simulated vaginal fluid. Microscopic images indicated presence of probiotics and oil globules enmeshed in the gelatin network. High viability (24.3 ± 0.46 × 108), germination upon application and a self-preserving nature were attributed to the optimum water activity (0.593 aw) of the developed composition. The retention of suppositories, germination of probiotics and their in vivo efficacy and safety in vulvovaginal candidiasis murine model are also reported.

12.
Chem Biol Interact ; 371: 110334, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36610610

ABSTRACT

A key signaling channel for the signal transduction of several crucial cytokines implicated in sepsis is the JAK/STAT system. Once cytokines attach to the proper receptors, JAK kinases linked to them are activated and can selectively phosphorylate STATs. Activated STATs subsequently go to the nucleus, where they play a key role in the transcription of the target genes. Various biological activities use the JAK/STAT pathway, including hematopoiesis, immunological modulation, cell differentiation, and apoptosis. Inflammatory lung illnesses affect people worldwide and are a serious public health concern. Numerous common respiratory conditions, such as asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome, are strongly influenced by inflammation. Microorganism infections or the destruction or demise of host cells are the causes of inflammation and the factors that perpetuate it. This review discusses the main elements of severe lung inflammation and how the JAK/STAT signaling pathway is essential for lung inflammation.


Subject(s)
Janus Kinases , Signal Transduction , Humans , Janus Kinases/metabolism , Signal Transduction/physiology , STAT Transcription Factors/metabolism , Cytokines/metabolism , Lung/metabolism , Inflammation
13.
J Water Health ; 20(12): 1673-1687, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36573672

ABSTRACT

Bacterial contamination of water and food is a grave health concern rendering humans quite vulnerable to disease(s), and proving, at times, fatal too. Exploration of the novel diagnostic tools is, accordingly, highly called for to ensure rapid detection of the pathogenic bacteria, particularly Escherichia coli. The current manuscript, accordingly, reports the use of silane-functionalized glass matrices and antibody-conjugated cadmium telluride (CdTe) quantum dots (QDs) for efficient detection of E. coli. Synthesis of QDs (size: 5.4-6.8 nm) using mercaptopropionic acid (MPA) stabilizer yielded stable photoluminescence (∼62%), corroborating superior fluorescent characteristics. A test sample, when added to antibody-conjugated matrices, followed by antibody-conjugated CdTe-MPA QDs, formed a pathogen-antibody QDs complex. The latter, during confocal microscopy, demonstrated rapid detection of the selectively captured pathogenic bacteria (10 microorganism cells/10 µL) with enhanced sensitivity and specificity. The work, overall, encompasses establishment and design of an innovative detection platform in microbial diagnostics for rapid capturing of pathogens in water and food samples.


Subject(s)
Biosensing Techniques , Cadmium Compounds , Quantum Dots , Humans , Escherichia coli , Tellurium , Bacteria , Water
14.
Crit Rev Ther Drug Carrier Syst ; 40(1): 49-100, 2022.
Article in English | MEDLINE | ID: mdl-36374841

ABSTRACT

Peptides are emerging as a promising candidate for therapeutic as well as diagnostic applications within the domain of clinical and scientific research. They are recognized for being highly selective, sensitive and efficacious with minimal or no toxicity. Small size, non-immunogenicity, ease of synthesis and huge scope of modification are some of the well-established properties of peptides, which make them an excellent alternative to not only small drug molecules but also to protein-based biopharmaceuticals such as antibodies and enzymes. The attractive pharmacological profile and intrinsic properties of peptides also make them an interesting diagnostic tool for imaging at the molecular and cellular levels. Molecular imaging coupled with targeted therapy using peptides as theranostics is a two-edged sword. Besides, traditional peptide formats, multifunctional newer peptide designs with improved pharmacokinetics and targetability are also being explored presently. In this review, we come up with a comprehensive summary of the latest progress on peptides and their potential applications in therapeutics and diagnosis for infectious and non-infectious diseases. The last part of the review discusses suitable carrier systems for the delivery of peptides along with highlighting the future challenges.


Subject(s)
Precision Medicine , Theranostic Nanomedicine , Humans , Theranostic Nanomedicine/methods , Drug Delivery Systems/methods , Molecular Imaging , Peptides
15.
Gut Pathog ; 14(1): 11, 2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35236424

ABSTRACT

BACKGROUND: There have been reports of patients suffering from typhoid fever, particularly those involving infants and immunocompromised patients, which at times present with Salmonella induced brain infection. Although rare, it has frequently been associated with adverse neurological complications and increased mortality. In this context, the gut-brain axis, involving two-way communication between the gut and the brain, holds immense significance as various gut ailments have been associated with psychiatric complications. In turn, several neurodegenerative diseases have been associated with an altered gut microbiota profile. Given the paucity of effective antimicrobials and increasing incidence of multi-drug resistance in pathogens, alternate treatment therapies such as probiotics have gained significant attention in the recent past. RESULTS: In the current study, prophylactic effect of Lactiplantibacillus plantarum (RTA 8) in preventing neurological complications occurring due to Salmonella brain infection was evaluated in a murine model. Along with a significant reduction in bacterial burden and improved histoarchitecture, L. plantarum (RTA 8) administration resulted in amelioration in the level of neurotransmitters such as serotonin, norepinephrine and dopamine in the gut as well as in the brain tissue. Simultaneously, increased gene expression of physiologically essential molecules such as mucin (MUC1 and MUC3) and brain-derived neurotrophic factor (BDNF) was also observed in this group. CONCLUSION: Present study highlights the potential benefits of a probiotic supplemented diet in improving various aspects of host health due to their multi-targeted approach, thereby resulting in multi-faceted gains.

16.
Sci Total Environ ; 831: 154857, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35351510

ABSTRACT

The contamination of food and potable water with microorganisms may cause food-borne and water-borne diseases. The common contaminants include Escherichia coli (E. coli), Salmonella sp. etc. The conventional methods for monitoring the water quality for the presence of bacterial contaminants are time-consuming, expensive, and not suitable for rapid on-spot detection in field conditions. In the current study, super paramagnetic iron oxide nanoparticles (SPIONs) were synthesized and conjugated with E. coli specific Aptamer I to detect E. coli cells qualitatively as well as quantitatively. The sludge consisting of E. coli- SPION complex was separated via magnetic separation. The presence of E. coli cells was confirmed with the help of standard techniques and confocal laser scanning microscopy (CLSM) employing Aptamer II conjugated CdTe-MPA quantum dots (QDs). Finally, an ATmega 328P prototype biosensor based on Aptamer II conjugated CdTe MPA QDs exhibited quantitative and qualitative abilities to detect E.coli. This prototype biosensor can even detect low bacterial counts (up to 1 × 102 cfu) with the help of a photodiode and plano-convex lens. Further, the prototype biosensor made up of ultraviolet light-emitting diode (UV LED), liquid crystal display (LCD) and ATmega328Pmicrocontroller offers on-spot detection of E.coli in water samples with high resolution and sensitivity. Similarly, this in-house developed prototype biosensor can also be utilized to detect bacterial contamination in food samples.


Subject(s)
Biosensing Techniques , Cadmium Compounds , Escherichia coli Infections , Magnetite Nanoparticles , Quantum Dots , Biosensing Techniques/methods , Escherichia coli , Humans , Quantum Dots/chemistry , Tellurium
17.
Drug Deliv Transl Res ; 12(7): 1659-1683, 2022 07.
Article in English | MEDLINE | ID: mdl-34993923

ABSTRACT

The study focused to evaluate and investigate optimized (using QbD) and novel ketoconazole (KTZ)-loaded solid lipid nanoparticles (KTZ-SLNs; 2% w/v KTZ) for enhanced permeation across skin. KTZ-SLNs were evaluated for size, distribution, zeta potential (ZP), percent entrapment efficiency (%EE), drug release, morphology (HRTEM and FESEM), thermal behaviour (DSC), spectroscopic (FTIR), and solid-state/diffraction characterization (X-ray diffraction, XRD). Moreover, ex vivo permeation and drug deposition into rat skin were conducted using Franz diffusion cell. The same was confirmed using human dermatome skin and fluorescence, confocal Raman, and vibrational ATR-FTIR microscopic methods. An in vivo dermatokinetics study was performed in rats to assess the extent of KTZ permeation into the skin. Stability including accelerated and photostability studies were conducted at different temperatures (2-8, 30, and 40 °C) for 12 months. The spherical, optimized KTZ-SLN formulation (KOF1) showed particle size of 293 nm and high EE of 88.5%. Results of FTIR, DSC, and XRD confirmed formation of KTZ-SLNs and their amorphous nature due to presence of KTZ in a dissolved state in the lipid matrix. In vitro release was slow and sustained whereas ex vivo permeation parameters were significantly high in KTZ-SLNs as compared to free drug suspension (KTZ-SUS) and marketed product (Nizral®; 2% KTZ w/v). Drug retention was 10- and five-fold higher than KTZ-SUS and marketed product, respectively. In vivo dermatokinetics parameters improved significantly with SLN formulation (410-900% enhanced). Confocal Raman spectroscopy experiment showed that KTZ-SLNs could penetrate beyond the human stratum corneum into viable epidermis. Fluorescent microscopy also indicated improved penetration of KTZ-SLNs. KTZ-SLNs were photostable and showed long-term stability over 12 months under set conditions.


Subject(s)
Ketoconazole , Nanoparticles , Animals , Drug Carriers/chemistry , Liposomes , Nanoparticles/chemistry , Particle Size , Rats , Suspensions
18.
Gels ; 8(1)2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35049593

ABSTRACT

Hydrogels, an advanced interactive system, is finding use as wound dressings, however, they exhibit restricted mechanical properties, macroscopic nature, and may not manage high exudate wounds or incorporate lipophilic actives. In this study, we developed a self-gelling solid lipid nanoparticle (SLNs) dressing to incorporate simvastatin (SIM), a lipophilic, potential wound-healing agent, clinically limited due to poor solubility (0.03 mg/mL) and absorption. The study explores unconventional and novel application of SIM. The idea was to incorporate a significant amount of SIM in a soluble form and release it slowly over a prolonged time. Further, a suitable polymeric surfactant was selected that assigned a self-gelling property to SLNs (SLN-hydrogel) so as to be used as a novel wound dressing. SLNs assign porosity, elasticity, and occlusivity to the dressing to keep the wound area moist. It will also provide better tolerance and sensory properties to the hydrogel. SIM loaded SLN-hydrogel was prepared employing an industry amenable high-pressure homogenization technique. The unique hydrogel dressing was characterized for particle size, zeta potential, Fourier transform infra-red spectroscopy, powder X-ray diffraction, differential scanning calorimetry, rheology, and texture. Significant loading of SIM (10% w/w) was achieved in spherical nanoparticule hydrogel (0.3 nm (nanoparticles) to 2 µm (gelled-matrix)) that exhibited good spreadability and mechanical properties and slow release up to 72 h. SLN-hydrogel was safe as per the organization for economic co-operation and development (OECD-404) guidelines, with no signs of irritation. Complete healing of excision wound observed in rats within 11 days was 10 times better than marketed povidone-iodine product. The presented work is novel both in terms of classifying a per se SLN-hydrogel and employing SIM. Further, it was established to be a safe, effective, and industry amenable invention.

19.
J Fungi (Basel) ; 7(12)2021 Dec 12.
Article in English | MEDLINE | ID: mdl-34947052

ABSTRACT

Fungi are reported to cause a range of superficial to invasive human infections. These often result in high morbidity and at times mortality. Conventional antifungal agents though effective invariably exhibit drug interactions, treatment-related toxicity, and fail to elicit significant effect, thus indicating a need to look for suitable alternatives. Fungi thrive in humid, nutrient-enriched areas. Such an environment is well-supported by the oral cavity. Despite this, there is a relatively low incidence of severe oral and periodontal fungal infections, attributed to the presence of antimicrobial peptides hosted by saliva, viz. histatin 5 (Hstn 5). It displays fungicidal activity against a variety of fungi including Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and unicellular yeast-like Saccharomyces cerevisiae. Candida albicans alone accounts for about 70% of all global fungal infections including periodontal disease. This review intends to discuss the scope of Hstn 5 as a novel recourse for the control of fungal infections.

20.
Expert Opin Drug Deliv ; 18(11): 1777-1789, 2021 11.
Article in English | MEDLINE | ID: mdl-34176401

ABSTRACT

BACKGROUND: Dermal disorders, owing to disruption of skin-microflora balance can be served by direct application of probiotics. However, there are few topical whole probiotic products in market because of (i) loss of viability during manufacturing and storage(ii) inadequate germination and retention on skin. Presently we report a novel (IPA 201811010395) emulgel incorporatingBacillus coagulans (Unique IS-2) for possible topical use. METHODS: Developed emulgel was characterized for particle size, texture, rheology, morphology, water activity, self-preservation, safety, and stability. RESULTS: We successfully incorporated 97 ± 5% (1.7×108CFU/g) Bacillus coagulans in honeycomb network of gelatin nanoparticles (≈600 nm). Maintenance of CFU at 30 ± 2°C, 65 ± 5% RH for 3 months confirmed viability of incorporated probiotic. Low water-activity (0.66-0.732aw) and challenge test (0.05-0.5% viability) confirmed its self-preserving nature. Early initiation (6 h) and complete (24 h) spore germination was evident onrabbit skin. No cytotoxicity, dermal irritation or translocation established its safety. Faster wound closure and reduced oxidative stress (LPO, catalase, SOD, glutathione reductase) in comparison to Soframycin® (1%w/w Framycetin) was observed in excision wound in mice. CONCLUSIONS: A whole cell probiotic formulation that is self-preserving, maintains probiotic viability, guarantees germination, and has wound healing properties was successfully formulated.


Subject(s)
Bacillus coagulans , Probiotics , Administration, Topical , Animals , Gelatin , Mice , Particle Size , Rabbits
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