Synthesis, classification and properties of hydrogels: their applications in drug delivery and agriculture.

Absorbent polymers or hydrogel polymer materials have an enhanced water retention capacity and are widely used in agriculture and medicine. The controlled release of bioactive molecules (especially drug proteins) by hydrogels and the encapsulation of living cells are some of the active areas of drug discovery research. Hydrogel-based delivery systems may result in a therapeutically advantageous outcome for drug delivery. They can provide various sequential therapeutic agents including macromolecular drugs, small molecule drugs, and cells to control the release of molecules. Due to their controllable degradability, ability to protect unstable drugs from degradation and flexible physical properties, hydrogels can be used as a platform in which various chemical and physical interactions with encapsulated drugs for controlled release in the system can be studied. Practically, hydrogels that possess biodegradable properties have aroused greater interest in drug delivery systems. The original three-dimensional structure gets broken down into non-toxic substances, thus confirming the excellent biocompatibility of the gel. Chemical crosslinking is a resource-rich method for forming hydrogels with excellent mechanical strength. But in some cases the crosslinker used in the synthesis of the hydrogels may cause some toxicity. However, the physically cross-linked hydrogel preparative method is an alternative solution to overcome the toxicity of cross-linkers. Hydrogels that are responsive to stimuli formed from various natural and synthetic polymers can show significant changes in their properties under external stimuli such as temperature, pH, light, ion changes, and redox potential. Stimulus-responsive hydrogels have a wider range of applications in biomedicine including drug delivery, gene delivery and tissue regeneration. Stimulus-responsive hydrogels loaded with multiple drugs show controlled and sustained drug release and can act as drug carriers. By integrating stimulus-responsive hydrogels, such as those with improved thermal responsiveness, pH responsiveness and dual responsiveness, into textile materials, advanced functions can be imparted to the textile materials, thereby improving the moisture and water retention performance, environmental responsiveness, aesthetic appeal, display and comfort of textiles. This review explores the stimuli-responsive hydrogels in drug delivery systems and examines super adsorbent hydrogels and their application in the field of agriculture.

ConjuPepDB: a database of peptide-drug conjugates.

Peptide-drug conjugates are organic molecules composed of (i) a small drug molecule, (ii) a peptide and (iii) a linker. The drug molecule is mandatory for the biological action, however, its efficacy can be enhanced by targeted delivery, which often also reduces unwanted side effects. For site-specificity the peptide part is mainly responsible. The linker attaches chemically the drug to the peptide, but it could also be biodegradable which ensures controlled liberation of the small drug. Despite the importance of the field, there is no public comprehensive database on these species. Herein we describe ConjuPepBD, a freely available, fully annotated and manually curated database of peptide drug conjugates. ConjuPepDB contains basic information about the entries, e.g. CAS number. Furthermore, it also implies their biomedical application and the type of chemical conjugation employed. It covers more than 1600 conjugates from ∼230 publications. The web-interface is user-friendly, intuitive, and useable on several devices, e.g. phones, tablets, PCs. The webpage allows the user to search for content using numerous criteria, chemical structure and a help page is also provided. Besides giving quick insight for newcomers, ConjuPepDB is hoped to be also helpful for researchers from various related fields. The database is accessible at: https://conjupepdb.ttk.hu/.

Decision tree analyses of key patient characteristics in Middle Eastern/North African and Latin American men treated with long-acting and short-acting PDE5 inhibitors for erectile dysfunction.

BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibitors have discontinuation rates as high as 60% in men with erectile dysfunction. Treatment satisfaction has been significantly associated with treatment continuation. Understanding key characteristics in terms of treatment preference, relationship, and lifestyle issues could provide direction on how to improve compliance with PDE5 inhibitor treatment globally. OBJECTIVE: The objective was to identify subgroups of interest in the pooled database of two observational studies conducted in Latin America (LA) and Middle East/North Africa (MENA) exploring patient characteristics and prescription of either a long- or short-acting PDE5 inhibitor at baseline. METHODS: Two identical prospective, non-interventional, observational, studies in MENA (N = 493) and LA (N = 511) treated men with an 'on demand' (pro re nata, PRN) PDE5 inhibitor (sildenafil, tadalafil, vardenafil, or lodenafil) during 6 months. In this post-hoc meta-analysis of two observational studies with equal design, pooled data were analyzed to determine patient characteristics and PDE5 inhibitor prescribed/used most likely to be associated with patient expectations, satisfaction, self-esteem, and patient-partner relationships. Decision tree analyses, with and without weighting, were used to identify and describe key features. RESULTS: In each analysis of patient expectations, patient-partner relationship, and self-esteem, we describe the two major subgroups at baseline for each decision tree. Analyses of patient expectations and sexual self-esteem revealed that patients prescribed long-acting PDE5 inhibitors (59%) highlighted the importance of treatment effect duration, second to partner satisfaction with treatment, while patients prescribed short-acting PDE5 inhibitors (32%) placed less importance on treatment effect duration but considerable importance on treatment effect lasting until intercourse completion. Further insights regarding patients, partner relationship characteristics, and treatment expectations were identified. CONCLUSION: Our analyses have described key characteristics, such as self- and partner perceptions, sexual attitudes, and treatment expectations in relation to the patients' country and prescribed treatment, which might guide treatment decisions in MENA and LA men with ED.

Two-photon absorption-controlled multidose drug release: a novel approach for secondary cataract treatment.

Tens of millions of cataract surgeries are done every year and the number is increasing heavily. Posterior capsule opacification is the major postoperative complication with an incidence of 10 to 50% within 5 years, depending on the age of the patient. We present a novel approach for secondary cataract treatment in a noninvasive manner. Photochemically triggered drug release from a polymer enables repeated drug applications for cataract treatment years after implantation of the intraocular lens, just when needed. However, light in the visible spectral range must pass through the lens but must not induce drug release. We demonstrate that two-photon absorption photochemistry is a powerful tool to overcome this problem. With wavelengths in the visible regime, a photochemical reaction that requires energies in the UV is triggered. The high intensities needed for this process never occur in any lighting condition in daily lives, but may be easily obtained with focused laser beams routinely used in ophthalmology. The properties of the therapeutic system are specified and the function is demonstrated by in-vitro cell tests. Noninvasive multidose photochemically triggered drug release from implanted intraocular lenses carrying a drug depot may be a therapeutic as well as an economic choice to established treatments of secondary cataracts.

Bioequivalence of a new sustained-release formulation of sodium valproate, valproate modified-release granules, compared with existing sustained-release formulations after once- or twice-daily administration.

STUDY OBJECTIVE: To compare the pharmacokinetic properties of valproate modified-release (MR) granules with those of two existing valproate sustained-release (SR) formulations to confirm their bioequivalence. DESIGN: Two randomized, open-label, two-period crossover studies under fasting conditions, and one open-label, randomized, single-dose, three-period crossover study under fasting and nonfasting conditions. Each study had a 7-day washout interval between periods. SETTING: Three hospitals in France. SUBJECTS: Healthy male Caucasian volunteers aged 18-35 years (27 subjects in study 1, 24 in study 2, and 24 in study 3). INTERVENTION: In studies 1 and 2, during two 15-day periods, subjects received either valproate MR granules or an existing valproate SR formulation. In study 3, subjects received only valproate MR granules 500 mg, once with water after a 10-hour fast, once with yogurt after a 10-hour fast, and once 30 minutes after a high-fat morning meal. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected, and pharmacokinetic parameters of valproic acid were determined for single-dose (studies 1-3) and repeated-dose (studies 1 and 2) administration. The 90% confidence intervals (CIs) for area under the concentration-time curve and maximum concentration (C max ) were in the acceptance limits for bioequivalence (i.e., 90% CI 0.80-1.25) after single and repeated doses of valproate MR granules administered once/day or twice/day. Although time to C max was slightly decreased with valproate MR granules, this difference did not induce a significant difference in terms of C max . Valproate MR granule formulation was bioequivalent with existing SR formulations. High-fat breakfast or yogurt did not modify either the bioavailability or pharmacokinetic profile of valproate MR granules. This formulation was well tolerated. The adverse event profile did not differ among the various regimens. CONCLUSION: Valproate MR granules, administered once/day or twice/day, may be an attractive alternative to existing SR formulations for patients who have difficulties with swallowing tablets or who favor granules over tablets.

Assuring quality and performance of sustained and controlled release parenterals: workshop report.

This is a summary report of the American Association of Pharmaceutical Scientists, the Food and Drug Administration and the United States Pharmacopoeia co-sponsored workshop on "Assuring Quality and Performance of Sustained and Controlled Release Parenterals." Experts from the pharmaceutical industry, the regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals and identify critical process parameters and their control. Areas were identified where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops, meetings and working groups in this area.

Reaçäo tecidual ao implante de um dispositivo de liberaçäo lenta (Periochip©) em dorso de rato albino / Tissue reaction at the implant of a slow release device (Periochip©) in albino rats

Os objetivos do presente trabalho foram verificar, através da revisäo da literatura, os resultados obtidos em estudos que utilizaram os dispositivos de liberaçäo lenta contendo clorexidina, assim como descrever a reaçäo tecidual ocorrida quando um dispositivo de liberaçäo lenta (PerioChip©) foi introduzido no tecido conjuntivo do dorso de ratos albinos. Foi possível constatar que o uso dos dispositivos de liberaçäo lenta contendo clorexidina representa um adjunto ao tratamento das doenças periodontais e, quando colocado no tecido conjuntivo do dorso do rato, provoca uma intensa reaçäo inflamatória