Papers by Jose Escobar-Chavez
Drug Design Development and Therapy, Apr 1, 2011
Journal of Pharmacy and Pharmaceutical Sciences, Mar 25, 2022
The transdermal route has been widely studied in the last decade due to its multiple advantages, ... more The transdermal route has been widely studied in the last decade due to its multiple advantages, where one of the most promising transdermal systems are microneedles, these allow the delivery of drugs in a painless way and with easy application, being very attractive for patients with chronic treatments. This review highlights the new research that develops this approach to transdermal therapies, including examples of materials and methods used for their manufacture and presenting an overview of the clinical trials currently available in Cochrane in a demonstrative way to understand the growing popularity of this strategy.
Polymers, Jun 8, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Pharmaceutics, May 31, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Springer eBooks, 2017
The use of ultrasound for the delivery of drugs through the skin is commonly known as sonophoresi... more The use of ultrasound for the delivery of drugs through the skin is commonly known as sonophoresis. The use of therapeutics and high frequencies of ultrasound for sonophoresis dates back to the 1950s, while low-frequency sonophoresis has only been investigated considerably during the past two decades. The use of ultrasound in therapeutics and drug delivery has gained significance in recent years; this is evident by the augment in patents filed and new commercial devices launched.
Springer eBooks, 2015
This work reflects the need to have information on physicochemical properties of pharmaceutical n... more This work reflects the need to have information on physicochemical properties of pharmaceutical nanoparticles and their interaction with biological systems, especially properties like particle size and surface functionalization that give special features when nanoparticles go through membranes, during opsonization, against immunogenicity, different toxicities, etc. This work aims to help new researchers to better understand the close relationship between pharmaceutical nanoparticles and their properties and their effects on biological systems and also contribute to nanotechnologists to take into account this situation and be aware that their responsibility does not end with the development and manufacture of these nanosystems. This chapter was written for specialist in different areas to enrich its content, and it is not the vision of a single author. We collaborated in this document nanotechnologists, toxicologists, and pharmaceutical technologists to give a critical approach to the imminent progress of nanotechnology in many areas of the knowledge such as pharmaceuticals, cosmetics, foods, chemical industry, computer industry, etc. Interaction of nanoparticles with human tissues, plants, animals, soils, water, air, etc. is inevitable because in the future, nanoparticles will be an important source of pollution and we must know how they interact with the surroundings depending on their physicochemical properties. Currently, a new branch of Nanotechnology called Nanotoxicology has been developed to deal with these dilemmas and in the future will be much more important than nowadays. Standardized protocols must be established to evaluate the cytotoxicity and genotoxicity caused by nanostructures.
BENTHAM SCIENCE PUBLISHERS eBooks, Mar 27, 2012
Pharmaceutical Chemistry Journal, Feb 1, 2021
The objective of this work was to develop a simple spectrophotometric method for determining anti... more The objective of this work was to develop a simple spectrophotometric method for determining antibiotic florfenicol in Eudragit nanocapsules. Regression curve of the method is linear in a concentration range of 80 – 480 μg/mL (correlation coefficient, 0.9998) at a selected wavelength of 270 nm. The limits of detection and quantification are 0.4 μg/mL and 1.2 μg/mL, respectively. The developed method demonstrated good inter-day and intra-day precision with RSD < 2. The percentage recovery of florfenicol was within 99.56 – 99.90%. In conclusion, the proposed method is specific, reproducible, accurate, and robust for the determination of florfenicol in Eudragit nanocapsules with detection at 270 nm in 95% confidence interval.
BENTHAM SCIENCE PUBLISHERS eBooks, Nov 23, 2016
PubMed, 2020
The development of a losartan potassium patch for the treatment of hypertension showed that a com... more The development of a losartan potassium patch for the treatment of hypertension showed that a combination of hydrophobic and hydrophilic polymers, using as a plasticizer citroflex and succinic acid as a cohesion promoter result in homogeneous films. The effect of the Eudragit® E100, PVP K30, citroflex and succinic acid in the bioadhesion, postwetting bioadhesion, resistance to rupture and drug release, was studied. The succinic acid in synergy with the plasticizer (citroflex) modifies the characteristics of the polymeric matrix of Eudragit® E100, increasing the release and the resistance to rupture of transdermal patches. For the case of the hydrophilic polymer PVP K30, it increases the bioadhesion and drug release by creating porous matrices. From a previous experimental design, the optimal formulation was acquired, and this formulation was physicochemically characterized. A transdermal patch was obtained with the next dimensions and characteristics: 28.46 ± 0.055 mm in diameter and 0.430 ± 0.008 mm in thickness, a bioadhesion of 1063.05 ± 60.33 gf, postwetting bioadhesion 995.9 ± 72.53 gf significantly decreased. The breaking strength was of 1301.5 ± 96.5 gf, surface pH patch of 6, constriction of 0% at 7 days, and 94.0366 ± 1.8617% of losartan content. The 93% of the drug is released at 4 h (n = 6), adjusting to the kinetic model of Higuchi and Peppas. In the in-vitro penetration studies by passive diffusion, a flow (J) of 42.2 μg/cm2h, a permeability constant (kp) of 2.1793E-03 cm/h and a latency time (tL) of 17.20 h and with the use of microneedles a flow (J) of 61.7 μg/cm2h, a permeability constant (kp) of 3.1869E-03 cm/h and a latency time (tL) of 17.74 h were obtained.
Journal of Pharmaceutical Innovation, Jul 30, 2019
The aim of this work was to optimize unidirectional buccal patches loaded with metoprolol (MT-MBP... more The aim of this work was to optimize unidirectional buccal patches loaded with metoprolol (MT-MBPs) to provide adequate mucoadhesive and water uptake properties as well as controlled drug release for the effective treatment of different cardiovascular diseases. Methods The patches were prepared layer-by-layer using the solvent casting method. A central composite design was employed to statistically optimize the formulation variables. Chitosan and Pluronic® F-127 (poloxamer 407) concentrations were chosen as the independent variables, while ex vivo mucoadhesive force, ex vivo residence time, in vitro water uptake (%), and in vitro drug release (%) were to be considered the dependent variables. The optimized formulation was also characterized and evaluated in terms of morphology, thermal behavior, tensile strength, elongation at break, and ex vivo drug permeation. Results The optimized MT-MBPs were successful in terms of mucoadhesive force (3.58 ± 0.62 N), residence time (342.67 ± 17.21 min), and water uptake at 1 h (24.53 ± 3.62%). A controlled drug release was obtained for 8 h. Thermal and morphologic analyses demonstrated that metoprolol was homogeneously distributed throughout the microporous chitosan-based polymer matrix. Furthermore, the MT-MBPs exhibited a tensile strength of 3.76 ± 0.55 N/mm 2 and an elongation at break of 36.52 ± 13.88%. The results of ex vivo permeation through pig buccal mucosa indicated that therapeutic metoprolol concentrations can be reached by using a patch of 5.62 cm 2. Conclusions Optimal composition of the MT-MBPs included 2.9% (w/v) and 2.6% (w/v) of chitosan and Pluronic® F-127, respectively, which constitutes the most suitable makeup for metoprolol buccal delivery.
International Journal of Pharmaceutics, Apr 1, 2009
The purpose of this work was to propose a drug delivery system based on a biodegradable porous me... more The purpose of this work was to propose a drug delivery system based on a biodegradable porous membrane, whose surface is covered by a nanoparticle film, thus achieving a controlled drug release rate. Furthermore, due to the fact that the assembly of the system is performed in aqueous medium, contact with organic solvents is avoided. The method is performed in two steps: (i) preparation of biodegradable porous membranes (by a solvent casting and particulate leaching technique) and biodegradable nanoparticles (by the emulsification-diffusion method), extensively eliminating the solvent in both of them; (ii) infiltration into membranes of an aqueous solution of a model drug (carbamazepine) and a nanoparticle dispersion. In both cases, poly(dl-lactic-co-glycolic acid) (PLGA 50:50) was used as a biodegradable polymer. Carbamazepine adsorbed onto biodegradable porous membranes shows an immediate release behavior (95% released in <15 min). Infiltration of different amounts of nanoparticles (50, 100, 400 and 600 mg of nanoparticles/0.625 g of membrane) into biodegradable porous membranes shows a Fickian diffusion according to Peppas model, and fits Higuchi's model. This behavior was attributed to the diffusional barrier constituted by the nanoparticle film. As expected, the carbamazepine release rate was dependent on the amount of infiltrated/adsorbed nanoparticles into biodegradable porous membrane. DSC studies show molecular dispersion of the drug throughout the membrane.
InTech eBooks, Oct 31, 2012
Recent Advances in Novel Drug Carrier Systems 202 is an open discussion, in one hand, the nanotec... more Recent Advances in Novel Drug Carrier Systems 202 is an open discussion, in one hand, the nanotechnologist continue making new and more sophisticated nanocarriers and in the other hand, toxicologist continue evaluating possible damaging effects. Whatever it happens, nanotechnology is the new era and nanomedicine cannot be taking off. New nanocarriers will be created and the entire scientist working in nanomedicine bet for it to be the cure of diseases that in this moment are difficult to deal with [3] The application of preparations to the skin for medical purposes is as old as the history of medicine itself, with references to the use of ointments and salves found in the records of Babylonian and Egyptian medicine. The historical development of permeation research is well described by Hadgraft & Lane [4]. Over time, the skin has become an important route for drug delivery in which topical, regional or systemic effects are desired. Nevertheless, skin constitutes an excellent barrier and presents difficulties for the transdermal delivery of therapeutic agents, since few drugs possess the characteristics required to permeate across the stratum corneum in sufficient quantities to reach a therapeutic concentration in the blood. In order to enhance drug transdermal absorption different methodologies have been investigated developed and patented [5,6]. Improvement in physical permeationenhancement technologies has led to renewed interest in transdermal drug delivery. Some of these novel advanced transdermal permeation enhancement technologies include: iontophoresis, electroporation, ultrasound, microneedles to open up the skin and more recently the use of transdermal nanocarriers [3,7-10]. A number of excellent reviews that have been published contain detailed discussions concerning many aspects of transdermal nanocarriers [11-17]. The present chapter shows an updated overview of the use of submicron particles and other nanostructures in the pharmaceutical field, specifically in the area of topical and transdermal drugs. This focus is justified due to the magnitude of the experimental data available with the use of these nanocarriers. The development of submicron particles and other nanostructures in the pharmaceutical and cosmetic fields has been emerged in the last decades for designing best formulations for application through the skin [18-21]. 2. The skin The skin is the largest organ of the body [22-24], accounting for more than 10% of body mass, and the one that enables the body to interact more intimately with its environment. Essentially, the skin consists of four layers: The SC, that is the outer layer of the skin (nonviable epidermis), and forms the rate-controlling barrier for diffusion for almost all compounds. It is composed of dead flattened, keratin-rich cells, the corneocytes. These dense cells are surrounded by a complex mixture of intercellular lipids, namely, ceramides, free fatty acids, cholesterol, and cholesterol sulphate. Their most important feature is that they are structured as ordered bilayer arrays [25-28]. The other layers are: the remaining layers of the epidermis (viable epidermis), the dermis, and the subcutaneous tissue (Figure 1). There are also several associated appendages: hair follicles sweat ducts, glands and nails [29,30].
International Journal of Nanomedicine, Aug 1, 2010
Solid lipid nanoparticles (SLNs) have been used for carrying different therapeutic agents because... more Solid lipid nanoparticles (SLNs) have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA) by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol ATO 888) and lauroyl macrogolglycerides (Gelucire 44/14) were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire ® , while it was difficult to obtain stable systems with Compritol ®. Systems with Gelucire ® were characterized by particle size, Z-potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content ($60 mg) in Gelucire SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid's partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown. The entrapment efficiency was higher than 92%, and CyA release from SLNs was relatively fast (99.60% in 45 min).
Journal of Pharmacy and Pharmaceutical Sciences, Apr 25, 2009
Transdermal drug delivery offers an attractive alternative to the conventional drug delivery meth... more Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. Ultrasound has been used extensively for medical diagnostics and to a certain extent in medical therapy (physiotherapy, ultrasonic surgery, hyperthermia). Nevertheless, it has only recently become popular as a technique to enhance drug release from drug delivery systems. A number of studies suggest the use of ultrasound as an external mean of delivering drugs at increased rates and at desired times. This review presents the main findings in the field of sonophoresis, namely transdermal drug delivery and transdermal monitoring. Particular attention is paid to proposed enhancement mechanisms and trends in the field of topical and transdermal delivery.
The Journal of Clinical Pharmacology, Nov 1, 2009
Transdermal drug delivery offers an attractive alternative to the conventional drug delivery meth... more Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of high-voltage pulses to the skin increases its permeability (electroporation) and enables the delivery of various substances into and through the skin. The application of electroporation to the skin has been shown to increase transdermal drug delivery. Moreover, electroporation, used alone or in combination with other enhancement methods, expands the range of drugs (small to macromolecules, lipophilic or hydrophilic, charged or neutral molecules) that can be delivered transdermally. The efficacy of transport depends on the electrical parameters and the physicochemical properties of drugs. The in vivo application of high-voltage pulses is well tolerated, but muscle contractions are usually induced. The electrode and patch design is an important issue to reduce the discomfort of the electrical treatment in humans. This review presents the main findings in the field of electroporation-namely, transdermal drug delivery. Particular attention is paid to proposed enhancement mechanisms and trends in the field of topical and transdermal delivery.
InTech eBooks, Mar 14, 2012
Chemical percutaneous enhancers have long been used to increase the range of drugs that can be ef... more Chemical percutaneous enhancers have long been used to increase the range of drugs that can be effectively delivered through the skin (López-Castellano & Merino, 2010). To date, a plethora of chemicals have been evaluated as enhancers, but their inclusion in topical or transdermal formulations is limited due to fact that the underlying mechanisms of action of these agents remain unclear. Although different chemicals are employed by the industry as percutaneous enhancers, some of which have several desirable properties, to date none has proved to be ideal. An ideal chemical penetration enhancer should have the following attributes (Barry, 1983; López-Castellano & Merino, 2010): a) It should be non-toxic, nonirritating and non-allergenic, b) It should work rapidly, and its activity and duration of effect should be both predictable and reproducible, c) It should exert no pharmacological activity within the body, d) It should work unidirectionally, e) When removed, the skin's barrier properties should return both rapidly and fully, f) It should be compatible with both excipients and drugs, and g) It should be cosmetically acceptable and, ideally, odourless and colourless. 2.1 Percutaneous penetration routes of drugs There are three major potential routes of percutaneous penetration: appendageal, transcellular (through the stratum corneum), and intercellular (through the stratum corneum) (Figure 1). There is a weight of evidence that suggests that passage through the intact stratum corneum constititutes the predominant route by which most molecules penetrate the skin, as the appendageal route is characterized by a limited available fractional Fig. 1. Processes of percutaneous absorption www.intechopen.com Chemical and Physical Enhancers for Transdermal Drug Delivery 399 a r e a o f 0. 1 %. I n t h i s w a y , d i f f u s i o n t h r o u g h t h e s k i n i s c o n t r o l l e d b y t h e p a r t i c u l a r characteristics of the stratum corneum. In order to obtain a sufficient drug flux and, in turn, the therapeutical objectives in question, an alternative is to use chemical percutaneous enhancers. These substances alter some of the properties of the stratum corneum. (López-Castellano & Merino, 2010) 2.2 Direct effects on the skin due to the use of transdermal penetration enhancers The lipid-protein-partititioning theory sets out the mechanisms by which enhancers alter skin lipids, proteins and/or partitioning behaviour (Barry, 1991): i) They act on the stratum corneum intracellular keratin by denaturing it or modifying its conformation, causing subsequent swelling and increased hydration; ii) They affect the desmosomes that maintain cohesion among corneocytes; iii) They modify the intercellular lipid domains to reduce the barrier-like resistance of the bilayer lipids. Disruption to the lipid bilayers can be homogeneous when the enhancer is distributed evenly within the complex bilayer lipids, but the accelerant is more likely to be heterogeneously concentrated within the domains of the bilayer lipids and iv) They alter the solvent nature of the stratum corneum, thus aiding the partitioning of the drug or a co-solvent into the tissue.(López-Castellano & Merino, 2010) 2.3 Indirect effects on the skin due to the use of transdermal penetration enhancers Chemical enhancers can produce: a) Modification of the thermodynamic activity of the vehicle. The permeation of a good solvent from the formulation, such as ethanol, can increase the thermodynamic activity of a drug; b) It has been suggested that, by permeating through the membrane, a solvent can 'drag' the permeant with it, though this concept is somewhat controversial and requires confirmation; c) Solubilising the permeant within the donor, especially when solubility is very low, as in the case of aqueous donor solutions, can reduce depletion effects and prolong drug permeation.(López-Castellano & Merino, 2010) 2.4 Classification of percutaneous chemical enhancers The classification of percutaneous enhancers is frequently based on the chemical class to which the compounds belong. Table 1 shows the principal classes of percutaneous enhancers. CHEMICAL CLASS COMPOUNDS Water Water Sulfoxides and similar chemicals Dimethyl sulfoxide, Dodecyl methyl sulfoxide Ureas Urea Alcohols Ethanol, Caprylic alcohol, Propylene glycol Pyrrolidones and derivatives N-methyl-2-pyrrolidone, 2-pyrrolidone Azone and derivatives Azone ® (1-dodecylazacycloheptan-2-one) Dioxolane derivatives SEPA ®
Journal of Pharmaceutical Innovation, Sep 26, 2020
The aim of this work was to develop and characterize biodegradable polymeric microneedle arrays l... more The aim of this work was to develop and characterize biodegradable polymeric microneedle arrays loaded with (i) losartan potassium powder and (ii) nanoparticles loaded with losartan potassium dispersed in polymeric matrix (starch/gelatin) as innovative pharmaceutical forms intended to be used for blood pressure control. Methods The lecithin/gelatin nanoparticles were prepared by desolvation method. The independent variables were lecithin/ gelatin amount and stirring speed while particle size, PDI (polydispersity index), and entrapment efficiency were the dependent variables studied. The optimized nanoparticle formulation was also characterized in terms of ζ potential and morphology. The mold of microneedle manufacture was created using a 3D printer by molding, and the microneedle arrays were prepared by micromolding method. The independent variables were starch/gelatin amount and drug form while fracture force, bioadhesion, and post-wetting bioadhesion were the dependent variables evaluated. The optimized microneedle array formulations were also characterized and evaluated in terms of morphology, release profiles, and in vitro losartan skin permeation studies. Results The optimized nanoparticle formulation was of 170.3 ± 3.1 nm of size, with 0.201 ± 0.013 of PDI, 40.45 ± 2.27% of entrapment efficiency, and − 32.9 ± 0.8 mV of ζ potential. The mold had an array of 25 microneedles with a height of 1.5 mm each. The optimized microneedle arrays were successful in terms of fracture force with a value of 408.3 ± 6.1 gf for MP and 320.2 ± 17.4 gf for MN. The results of in vitro skin permeation studies indicated that therapeutic losartan concentrations can be reached by using a microneedle array of 49 cm 2 for MP and 13 cm 2 for MN. Conclusion The optimal formulation of the microneedle array with nanoparticles constitutes the most suitable option for skin losartan delivery.
Drug Development and Industrial Pharmacy, Nov 20, 2009
Mycetoma is a chronic, degenerative, and incapacitating infection of the skin and subcutaneous ti... more Mycetoma is a chronic, degenerative, and incapacitating infection of the skin and subcutaneous tissue. This study focuses on developing a kanamycin-based auxiliary system intended to be used in the treatment of mycetoma caused by Actinomadura madurae. Transdermal patches (with two different formulations: one with free kanamycin [K] and the other one with kanamycin adsorbed in silica [K-SG]) and an emulgel were developed. Both patches were prepared by the casting-evaporation technique. To characterize them, differential scanning calorimetry, bioadhesion, post-moisture detachment, strength and rupture distance, gas exchange, water uptake, and dissolution studies were carried out. The emulgel (containing 0.57% of kanamycin) was prepared from an oil-in-water emulsion, which was then incorporated to a gel. the patches with the best characteristics contained 22.9% of silica and 14.6% of kanamycin. Dissolution studies indicated that 8.8% of kanamycin released from K and 3.2% from K-SG at 24h. The emulgel containing 0.57% of kanamycin showed good technological characteristics for its application to the skin (viscosity, 44.9 +/- 1.4 poises; pH, 6.9 +/- 0.4; and penetrability, 52.7 +/- 5.1). The optimal patches were those containing 15.9% of freely dispersed kanamycin (K) and 14.6% of kanamycin adsorbed in silica (K-SG), which corresponds to the batch 2-0.8. The assessments performed to both pharmaceutical forms (patches and emulgel) show that they have the adequate technological characteristics for being used as an auxiliary in the treatment of actinomycetoma caused by A. madurae.
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Papers by Jose Escobar-Chavez