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Hypertrophic scars and keloids are characterized by an excessive collagen deposition. The available treatment options are invasive and can result in recurrence of scar formation. Using liposomes and transferosomes for the topical delivery of papain, a proteolytic enzyme, can be effective treatment. The objective of the study is to formulate papain-loaded liposomes and transferosomes, characterize the formulations, and study in vitro permeation using shed snake skin and Sprague-Dawley rat skin as models for stratum corneum and full thickness skin. Papain-loaded liposomes and transferosomes were formulated using the thin-film hydration method for the delivery of papain across the stratum corneum barrier. An in vitro permeation study carried out using shed-snake skin and Sprague-Dawley rat skin models showed that transferosomes were able to deliver papain across the stratum corneum barrier, while papain solution and papain liposomes were not able to cross the barrier. However, transferosomes were not able to deliver papain across the full thickness rat skin model suggesting the deposition of papain loaded transferosomes in the epidermal or dermal layer of skin. In addition, an ex-vivo model was used to analyze the effect of papain exposure on the morphology of the epidermis taken from rat skin exposed to papain solution, papain in transferosomes and papain in liposomes. Papain in solution resulted in a noticeable degradation of the epidermis, but when embedded in either transferosomes or liposomes there was no noticeable change when compared to control animals. The cytotoxicity study performed using HeLa cells showed that the cells were viable at papain concentrations lower than 0.01 mg/ml.
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Cicatriz Hipertrófica , Queloide , Humanos , Ratas , Animales , Liposomas/uso terapéutico , Queloide/tratamiento farmacológico , Queloide/patología , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/patología , Papaína , Ratas Sprague-Dawley , Células HeLa , Administración CutáneaRESUMEN
Breast cancer is the most diagnosed type of cancer, with 2.26 million cases and 685,000 deaths recorded in 2020. If left untreated, this deadly disease can metastasize to distant organs, which is the reason behind its incurability and related deaths. Currently, conventional therapies are used to treat breast cancer, but they have numerous shortcomings such as low bioavailability, short circulation time, and off-target toxicity. To address these challenges, nanomedicines are preferred and are being extensively investigated for breast cancer treatment. Nanomedicines are novel drug delivery systems that can improve drug stability, aqueous solubility, blood circulation time, controlled release, and targeted delivery at the tumoral site and enhance therapeutic safety and effectiveness. Nanoparticles (NPs) can be administered through different routes. Although the injectable route is less preferred than the oral route for drug administration, it has its advantages: it helps tailor drugs with targeted moiety, boosts payload, avoids first-pass metabolism, and improves the pharmacokinetic parameters of the active pharmaceutical ingredients. Targeted delivery of nanomedicine, closer to organelles such as the mitochondria and nuclei in breast cancer, reduces the dosage requirements and the toxic effects of chemotherapeutics. This review aims to provide the current status of the recent advances in various injectable nanomedicines for targeted treatment of breast cancer.
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Spinal cord injury (SCI) is characterized by mechanical injury or trauma to the spinal cord. Currently, SCI treatment requires extremely high doses of neuroprotective agents, which in turn, causes several adverse effects. To overcome these limitations, the present study focuses on delivery of a low but effective dose of a naturally occurring antioxidant, α-tocopherol (α-TP). Calcium alginate nanoparticles (CA-NP) and poly D,L-lactic-co-glycolic acid nanoparticles (PLGA-NP) prepared by ionotropic gelation and solvent evaporation technique had particle size of 21.9 ± 11.19 and 152.4 ± 10.6 nm, respectively. Surface morphology, surface charge, as well as particle size distribution of both nanoparticles were evaluated. Entrapment of α-TP into CA-NP and PLGA-NP quantified by UPLC showed entrapment efficiency of 4.00 ± 1.63% and 76.6 ± 11.4%, respectively. In vitro cytotoxicity profiles on human astrocyte-spinal cord (HA-sp) showed that blank CA-NP at high concentrations reduced the cell viability whereas blank PLGA-NP showed relatively safer cytotoxic profiles. In addition, PLGA nanoparticles encapsulated with α-TP (α-TP-PLGA-NP) in comparison to α-TP alone at high concentrations were less toxic. Pretreatment of HA-sp cells with α-TP-PLGA-NP showed two-fold higher anti-oxidative protection as compared to α-TP alone, when oxidative stress was induced by H2O2. In conclusion, CA-NP were found to be unsuitable for treatment of SCI due to their cytotoxicity. Comparatively, α-TP-PLGA-NP were safer and showed high degree of protection against oxidative stress than α-TP alone.
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Nanopartículas , Traumatismos de la Médula Espinal , Portadores de Fármacos/uso terapéutico , Humanos , Peróxido de Hidrógeno , Ácido Láctico , Estrés Oxidativo , Tamaño de la Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , alfa-TocoferolRESUMEN
Ultra-long-acting integrase strand transfer inhibitors were created by screening a library of monomeric and dimeric dolutegravir (DTG) prodrug nanoformulations. This led to an 18-carbon chain modified ester prodrug nanocrystal (coined NM2DTG) with the potential to sustain yearly dosing. Here, we show that the physiochemical and pharmacokinetic (PK) formulation properties facilitate slow drug release from tissue macrophage depot stores at the muscle injection site and adjacent lymphoid tissues following single parenteral injection. Significant plasma drug levels are recorded up to a year following injection. Tissue sites for prodrug hydrolysis are dependent on nanocrystal dissolution and prodrug release, drug-depot volume, perfusion, and cell-tissue pH. Each affect an extended NM2DTG apparent half-life recorded by PK parameters. The NM2DTG product can impact therapeutic adherence, tolerability, and access of a widely used integrase inhibitor in both resource limited and rich settings to reduce HIV-1 transmission and achieve optimal treatment outcomes.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Profármacos , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Oxazinas/uso terapéutico , Piperazinas , Profármacos/farmacología , Piridonas/uso terapéuticoRESUMEN
Aim: A polymeric in situ gelling delivery system for localized and sustained delivery to jawbone infections was developed. Materials & methods:In situ gelling delivery systems were prepared using either Poly(dl-lactic acid) or chitosan and Pluronic F127/Pluronic F68. Metronidazole nanoparticles were prepared using poly(dl-lactide-co-glycolide) or chitosan. Poly(dl-lactide-co-glycolide) was used for microparticles. Particles were characterized for size, charge and morphology. Results: Viscosity and yield stress of the gels were 0.4 Pa.s and 2 Pa, respectively, with 70% cell viability over 72 h. Around 90% of loaded metronidazole was released at a sustained rate over 1 week. Conclusion: Use of appropriate amount of nano/microparticles in the gel resulted in a sustained release over a period of 1 week - needed for jawbone infection.
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GelesRESUMEN
In vitro diffusion testing of topical formulations has long been examined using Franz diffusion chambers, however, Franz chambers are typically used with relatively large volumes, lack the air/membrane interface present in vivo, and do not account for changes in formula characteristics as solvent evaporates. Here we present our patented Munt-Dash diffusion chamber designed for direct spray application onto a model membrane. Diffusion characteristics from topical spray formulations utilizing both the Munt-Dash chamber and Franz diffusion chambers were evaluated and compared. Using diclofenac sodium and lidocaine hydrochloride as model drugs and shed snakeskin as a model for stratum corneum, test solutions were applied to Franz diffusion chambers using a pipette and to the Munt-Dash chamber using a high-speed syringe pump and sprayer. Both chambers presented permeability data consistent with previously reported in vitro and in vivo studies. Significant differences were observed in permeability by formulation and temperature. This suggests that although Franz chambers produce relevant data, the failure to account for small volumes and drying during application may produce misleading results. The Munt-Dash chamber may improve in vitro testing by providing these factors. This data suggests the Munt-Dash chamber is a suitable alternative to the Franz chamber for topical spray formulations.
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Epidermis , Piel , Difusión , Cámaras de Difusión de Cultivos , Técnicas In Vitro , PermeabilidadRESUMEN
BACKGROUND: Numerous studies have demonstrated the efficacy of creatine supplementation for improvements in exercise performance. Few studies, however, have examined the effects of phosphocreatine supplementation on exercise performance. Furthermore, while polyphenols have antioxidant and anti-inflammatory properties, little is known regarding the influence of polyphenol supplementation on muscular strength, power, and endurance. Thus, the purpose of the present study was to compare the effects of 28 days of supplementation with phosphocreatine disodium salts plus blueberry extract (PCDSB), creatine monohydrate (CM), and placebo on measures of muscular strength, power, and endurance. METHODS: Thirty-three men were randomly assigned to consume either PCDSB, CM, or placebo for 28 days. Peak torque (PT), average power (AP), and percent decline for peak torque (PT%) and average power (AP%) were assessed from a fatigue test consisting of 50 maximal, unilateral, isokinetic leg extensions at 180°·s- 1 before and after the 28 days of supplementation. Individual responses were assessed to examine the proportion of subjects that exceeded a minimal important difference (MID). RESULTS: The results demonstrated significant (p < 0.05) improvements in PT for the PCDSB and CM groups from pre- (99.90 ± 22.47 N·m and 99.95 ± 22.50 N·m, respectively) to post-supplementation (119.22 ± 29.87 N·m and 111.97 ± 24.50 N·m, respectively), but no significant (p = 0.112) change for the placebo group. The PCDSB and CM groups also exhibited significant improvements in AP from pre- (140.18 ± 32.08 W and 143.42 ± 33.84 W, respectively) to post-supplementation (170.12 ± 42.68 W and 159.78 ± 31.20 W, respectively), but no significant (p = 0.279) change for the placebo group. A significantly (p < 0.05) greater proportion of subjects in the PCDSB group exceeded the MID for PT compared to the placebo group, but there were no significant (p > 0.05) differences in the proportion of subjects exceeding the MID between the CM and placebo groups or between the CM and PCDSB groups. CONCLUSIONS: These findings indicated that for the group mean responses, 28 days of supplementation with both PCDSB and CM resulted in increases in PT and AP. The PCDSB, however, may have an advantage over CM when compared to the placebo group for the proportion of individuals that respond favorably to supplementation with meaningful increases in muscular strength.
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Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Fosfocreatina/farmacología , Resistencia Física/efectos de los fármacos , Extractos Vegetales/farmacología , Arándanos Azules (Planta)/química , Creatina , Suplementos Dietéticos , Método Doble Ciego , Humanos , Masculino , Torque , Adulto JovenRESUMEN
The topical and transdermal routes of drug administration are long known to the field of pharmaceutics. These routes have been explored for the delivery of a wide range of therapeutic agents over centuries. However, the anatomy of the skin and the physicochemical properties of molecules limit their transport via these routes. To overcome these challenges, a nano-phospholipid carrier called liposome was developed in the 1960s. Liposomal delivery of drugs was reported to be limited to the upper layers of skin. This led to the development of self-regulating and self-adaptable vesicles known as transfersomes. This review critically evaluates the barriers in delivery across the skin, recent advancements in liposomes, transfersomes and their impact in the pharmaceutical field.
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Liposomas , Absorción Cutánea , Administración Cutánea , Sistemas de Liberación de Medicamentos , Liposomas/metabolismo , Fosfolípidos , Piel/metabolismoRESUMEN
This study reports the development of a binary drug delivery system consisting of charged liposomes and an oppositely charged peptide-photosensitiser conjugate. Liposomes were prepared with phosphatidyl-l-serine as a negatively charged lipid. Calcein, a fluorophore marker, and doxorubicin, an anticancer drug, were used as model hydrophilic loads. The conjugate consisted of a positively charged arginine-rich peptide synthesised by solid-phase peptide synthesis, and a phthalocyanine derivative with characteristic absorption around 685 nm. Illumination of the binary system with far-red light of 12-15 mW/cm2 intensity resulted in 5- to 15-fold increase in release of payloads from the liposomes. The mechanism of drug release was based on photosensitised oxidation of lipids destabilising the liposomal membrane. The cytotoxicity of the liposomes loaded with doxorubicin was tested on B16-F10 melanoma and Y79 retinoblastoma cells. The cytotoxicity of the illuminated binary system in melanoma cell line was significantly higher as compared to the system without illumination. The components of the binary system can be individually prepared and stored with greater storage stability. However, their combination will allow for substantial release of hydrophilic payload from the liposomes under externally applied light.
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Doxorrubicina/química , Liberación de Fármacos/efectos de la radiación , Fluoresceínas/química , Luz , Liposomas/química , Péptidos/síntesis química , Secuencia de Aminoácidos , Sistemas de Liberación de Medicamentos , Fluorescencia , Humanos , Péptidos/químicaRESUMEN
Over the last several decades, nanoparticulate delivery systems have emerged as advanced drug and gene delivery tools for cancer therapy. However, their translation into clinical use still poses major challenges. Even though many innovative nanoparticulate approaches have shown very positive results both in vitro and in vivo, few of them have found a place in clinical practice. Possible factors responsible for the existing gap in the translation of nanomedicine to clinical practice may include oversimplification of enhanced permeability and retention effect, lack of correlation between the in vivo animal data vs their translation in human, and challenging multiple biological steps experienced during systemic delivery of nanomedicine. Understanding these challenges and coming up with solutions to overcome them is an important step in effective translation of nanomedicine into clinical practice. This review focuses on advancements in the field of nanomedicine used for anti-cancer therapy, including passive targeting, active targeting, and stimuli-controlled delivery. The review further reveals some of the challenges that are currently faced by pharmaceutical scientists in translation of nanomedicine; these include lack of adequate models for preclinical testing that can predict efficacy in humans, absence of appropriate regulatory guidelines for their approval processes, and difficulty in scale-up of the manufacturing of nanodrug delivery systems. A better understanding of these challenges will help us in filling the gap between the bench and bedside in cancer therapy.
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Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Nanomedicina , Neoplasias/terapia , Animales , Humanos , Nanomedicina/métodosRESUMEN
Light-induced drug release has been explored as a strategy for externally modulating the release of drug from delivery systems. This study reports the development of a solid lipid nanoparticulate system (SLN) for paclitaxel (PTX), where photosensitizer-mediated oxidation of lipids was used as a mechanism for controlling the drug release. Low-intensity (23 mW/cm2) near-infrared (around 730 nm) illumination was externally applied as the light source. PTX release was less than 10% within 4 h from these SLN and was 8-fold higher after application of light at time zero. The other advantages of this approach include the use of ascorbic acid (ASC) as an antioxidant for enhancing the release and storage stability of the delivery system. Antioxidant like ASC in the SLN decrease the degradation of lipid by 8-fold within 4 months of storage. Presence of ASC and light illumination of SLN containing PTX further decreased the IC50 by 2 times in A549 cells. The uniqueness of this approach allows the possibility of external modulation to achieve pulsatile release from the delivery system. The light used in the NIR spectral range of 700-850 nm, which has the greatest tissue penetration ability, with a low intensity will be safe for normal tissues.
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Antineoplásicos Fitogénicos/administración & dosificación , Lípidos/química , Nanopartículas , Paclitaxel/administración & dosificación , Células A549 , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Ácido Ascórbico/química , Preparaciones de Acción Retardada , Liberación de Fármacos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Concentración 50 Inhibidora , Luz , Paclitaxel/farmacología , Factores de TiempoRESUMEN
The poor pharmacokinetic parameters and low solubility of many anticancer therapeutics have warranted the use of drug-delivery systems such as liposomes. Overcoming some drawbacks of the conventional liposomes, targeted liposomal delivery by longer circulation time by addition of poly(ethylene glycol) to the liposomal surface and further adding specific ligands to achieve ligand selective retention and uptake has been introduced. PEGylated liposomes are the only second-generation liposomal formulations in clinical use and are now being challenged with the allergenic response they pose even in the treatment of naive patients. This article will review the challenges and hindrances in the use of long circulating liposomes and explore the opportunities to overcome this issue.
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Antineoplásicos/administración & dosificación , Composición de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Polietilenglicoles/química , Animales , Antineoplásicos/farmacocinética , Modelos Animales de Enfermedad , Composición de Medicamentos/tendencias , Semivida , Humanos , Liposomas , Solubilidad , Factores de TiempoRESUMEN
The objective of this study was to develop a nanodelivery system containing a mucoadhesive polymer hyaluronic acid (HA) for oral delivery. Metformin was used as a model drug. Blank and drug-loaded HA nanostructures were prepared by precipitation method and characterized for particle size (PS), zeta potential (ZP), physical stability (over 65 days), surface morphology, moisture content, and physical state of the drug in the nanostructures. The cytotoxicity and hemolysis potential of the delivery system was assessed in Caco-2 cells and whole human blood, respectively. The in vitro release of metformin and its uptake in Caco-2 cells was evaluated using high-performance liquid chromatography. Ex vivo permeability of metformin was measured through goat intestinal membrane. The nanoparticles were physically stable and neutrally charged with an average PS of 114.53 ± 12.01 nm. This nanodelivery system existed as nanofibers containing metformin in a crystalline state. This delivery system released the drug rapidly with > 50% of metformin released within 1 h. Cellular uptake studies on Caco-2 cells indicated higher uptake of metformin from nanoparticle as compared to metformin in solution, up to first 45 min. Ex vivo permeability studies on the other hand showed a higher metformin permeability from solution relative to that from nanoparticles through the goat intestinal membrane. Metformin nanoparticles were non-toxic at therapeutic concentrations in Caco-2 cells and showed no hemolytic effect to RBCs. This study indicates the preparation, characterization, as well as the potential use of HA nanostructures for oral delivery.
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Sistemas de Liberación de Medicamentos , Ácido Hialurónico/administración & dosificación , Metformina/administración & dosificación , Administración Oral , Animales , Células CACO-2 , Sistemas de Liberación de Medicamentos/métodos , Humanos , Ácido Hialurónico/química , Metformina/química , Metformina/farmacocinética , Nanoestructuras/administración & dosificación , PermeabilidadRESUMEN
Curcumin and resveratrol are naturally occurring polyphenolic compounds having anti-cancer potential. However, their poor aqueous solubility and bioavailability limit their clinical use. Entrapment of hydrophobic drugs into hydrophilic nanoparticles such as calcium alginate presents a means to deliver these drugs to their target site. Curcumin and resveratrol-loaded calcium alginate nanoparticles were prepared by emulsification and cross-linking process. The nanoparticles were characterized for particle size, zeta potential, moisture content, physical state of the drugs, physical stability, and entrapment efficiency. An UPLC method was developed and validated for the simultaneous analysis of curcumin and resveratrol. Alginate nanoformulation was tested for in vitro efficacy on DU145 prostate cancer cells. The particle size of the nanosuspension and freeze-dried nanoparticles was found to be 12.53 ± 1.06 and 60.23 ± 15 nm, respectively. Both DSC and powder XRD studies indicated that curcumin as well as resveratrol were present in a non-crystalline state, in the nanoparticles. The entrapment efficiency for curcumin and resveratrol was found to be 49.3 ± 4.3 and 70.99 ± 6.1%, respectively. Resveratrol showed a higher percentage of release than curcumin (87.6 ± 7.9 versus 16.3 ± 3.1%) in 24 h. Curcumin was found to be taken up by the cells from solution as well as the nanoparticles. Resveratrol had a poor cellular uptake. The drug-loaded nanoparticles exhibit cytotoxic effects on DU145 cells. At high concentration, drug solution exhibited greater toxicity than nanoparticles. The alginate nanoformulation was found to be safe for intravenous administration.
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Alginatos/química , Antineoplásicos/administración & dosificación , Curcumina/administración & dosificación , Nanopartículas/química , Neoplasias de la Próstata/tratamiento farmacológico , Estilbenos/administración & dosificación , Línea Celular Tumoral , Curcumina/química , Curcumina/farmacología , Liberación de Fármacos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Masculino , Tamaño de la Partícula , Neoplasias de la Próstata/patología , Resveratrol , Estilbenos/química , Estilbenos/farmacologíaRESUMEN
Unprotected sunlight exposure is a risk factor for a variety of cutaneous cancers. Topically used dihydroxyacetone (DHA) creates, via Maillard reaction, chemically fixed keratin sunscreen in the stratum corneum with significant protection against UVA/Soret radiation. When used in conjunction with naphthoquinones a naphthoquinone-modified DHA Maillard reaction is produced that provides protection across the UVB/UVA/Soret spectra lasting up to 1 week, resisting sweating and contact removal. The aim of this study was to examine a simplified version of this formulation for effect on UV transmission and to determine if penetration levels merit toxicity concerns. Permeability was demonstrated for freshly prepared DHA (30 mg/mL) and lawsone (0.035 mg/mL) alone and in combination using a side-by-side diffusion apparatus at 37°C over 48 h across shed snake skin and dermatomed pig skin. These samples were then examined for effectiveness and safety. Concentrations were determined by HPLC and UPLC monitored from 250-500 nm. Lawsone flux significantly decreased across pig skin (20.8 (± 4.8) and 0.09 (± 0.1) mg/cm(2) h without and with DHA, respectively) but did not change across shed snake skin in the presence of DHA. Significantly reduced lawsone concentration was noted in donor chambers of combined solutions. Damage was not observed in any skins. Darker coloration with greater UV absorbance was observed in skins exposed to the combined solution versus individual solutions. This study confirmed that combined DHA and lawsone provided effective blocking of ultraviolet light through products bound in keratinized tissue. DHA permeation levels in pig skin suggest further in vitro and in vivo study is required to determine the safety of this system.
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Dihidroxiacetona/administración & dosificación , Naftoquinonas/administración & dosificación , Piel/efectos de los fármacos , Protectores Solares/administración & dosificación , Animales , Boidae/metabolismo , Difusión , Porcinos , Rayos UltravioletaRESUMEN
AIM: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing both paclitaxel (PTX) and gemcitabine hydrochloride (GEM) were prepared and the effect of lyophilization and spray drying on physicochemical characteristics of these nanoparticles were evaluated. METHODS: Nanoemulsions were prepared by oil-in-water emulsion solvent diffusion technique using sonication and high-pressure homogenization. Nanoemulsion was dried using lyophilization or spray drying and drug content analyzed by high-performance liquid chromatography (HPLC). RESULTS: The particle size of the nanoemulsion was 183.6 ± 10.8 nm and the entrapment efficiency for PTX and GEM was 72.01 ± 1.35% and 6.95 ± 3.97%. Many properties including particle size, stability, surface morphology, moisture content, release characteristic and cellular uptake in MDCK and MDA-MB-231 cells were affected by the method of drying. CONCLUSION: The lyophilized nanoparticles were smaller in size with higher stability and cellular uptake than spray-dried nanoparticles.
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Antineoplásicos/administración & dosificación , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Rastreo Diferencial de Calorimetría , Sistemas de Liberación de Medicamentos , Estabilidad de Medicamentos , Liofilización , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía de Fuerza Atómica , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , SolubilidadRESUMEN
The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/síntesis química , Nanocápsulas/química , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Difusión , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Humanos , Masculino , Nanocápsulas/administración & dosificación , Nanocápsulas/ultraestructura , Células Madre Neoplásicas/patología , Paclitaxel/administración & dosificación , Paclitaxel/química , Tamaño de la Partícula , Neoplasias de la Próstata/patología , Resultado del Tratamiento , Alcaloides de Veratrum/administración & dosificación , Alcaloides de Veratrum/químicaRESUMEN
AIM: The objective of this study was to investigate the influence of the high-pressure homogenization (HPH) process and stabilizers on the physicochemical properties of glycerol monooleate (GMO)/chitosan nanostructures using curcumin as a model hydrophobic drug. MATERIALS & METHODS: The oil-in-water nanoemulsion of the GMO/chitosan system was prepared by sonication and HPH techniques using two different stabilizers (polyvinyl alcohol [PVA] and poloxamer 407). The particle size (PS), ζ-potential (ZP) and physical stability of the nanoemulsion were investigated. These nanoemulsions were lyophilized and characterized for PS, ZP, surface morphology, moisture content and physical form of the drug in the nanostructures. The in vitro release and the uptake of curcumin in Caco-2 cells were evaluated using an ultra-performance liquid chromatography method. RESULTS: Three cycles of HPH produced a 50-65% reduction in the PS of the nanoemulsion. A change in stabilizer, from PVA to poloxamer, did not affect the PS, physical stability, moisture content or the physical form of the drug in the formulation. However, there was a significant change in the ZP, surface morphology, in vitro release rate and cellular uptake from the two formulations. CONCLUSION: The process of HPH effectively reduces the PS of the GMO/chitosan nanoemulsions loaded with the hydrophobic drug. The type of stabilizer used affects several physicochemical properties of the GMO/chitosan nanostructures. Compared with PVA, poloxamer 407 is a more effective stabilizer for stabilizing the GMO/chitosan system containing a hydrophobic drug nanoemulsion at low concentrations.
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Antineoplásicos/administración & dosificación , Quitosano/química , Curcumina/administración & dosificación , Portadores de Fármacos/química , Excipientes/química , Glicéridos/química , Nanoestructuras/química , Antineoplásicos/farmacocinética , Células CACO-2 , Curcumina/farmacocinética , Humanos , Poloxámero/química , Alcohol Polivinílico/química , PresiónRESUMEN
AIMS: The present research focuses on the development of the surface modified solid lipid nanoparticulate (SLN) system for enhancing the stability and sustaining the release of a model hydrophilic drug ifosfamide. MATERIALS & METHODS: SLNs consisting of glyceryl monooleate (GMO) and chitosan were prepared by double emulsion technique, crosslinked with sodium tripolyphosphate, followed by lyophilization under two different vacuum conditions. The physicochemical characterization of SLNs included evaluation of surface morphology, particle size and surface charge, moisture content and physical state of the drug in the delivery system. The in vitro drug release and the stability were evaluated using high-performance liquid chromatography and liquid chromatography/mass spectrometry, respectively. Cellular permeability and subcellular localization studies were performed using Caco-2 cells. RESULTS: Different chamber pressures during lyophilization produced SLNs with different morphologies and moisture contents. SLNs demonstrated high encapsulation efficiency, sustained release, and enhanced stability of ifosfamide with a high cellular uptake and permeability for Caco-2 cells. CONCLUSION: GMO and chitosan SLNs could be successfully used for enhancing the stability, sustaining the release, enhancing the targeting and permeability characteristics of ifosfamide.
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Ifosfamida/química , Lípidos/química , Nanopartículas/química , Células CACO-2 , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Quitosano/química , Cromatografía Líquida de Alta Presión , Glicéridos/química , Humanos , Ifosfamida/farmacocinética , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , TermogravimetríaRESUMEN
AIMS: This investigation compared the tumor distribution, efficacy, blood pharmacokinetic parameters and hematological alterations following treatment with chitosan/glyceryl-monooleate (GMO) nanostructures containing paclitaxel (PTX) to a conventional formulation of PTX (Taxol(®)) in BALB/c female mice. MATERIALS & METHODS: The tumor and blood concentrations of PTX were evaluated by HPLC and the pharmacokinetic parameters were determined through noncompartmental methods. Tumor development was evaluated by histopathological methods and hematological composition was monitored through differential white blood cells counts. RESULTS: Lower localized or intravenous doses of PTX-chitosan/GMO nanostructures significantly increased the antitumor activity of paclitaxel. The tumor distribution studies showed effective concentrations in the tumors with the chitosan/GMO formulation while systemic blood levels remained lower than after administration of the conventional formulation. CONCLUSION: Delivery systems consisting of chitosan/GMO and PTX are safe and effective administered locally (intratumorally) or intravenously.