Transdermal patches: Design and current approaches to painless drug delivery

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation

Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E 2 and F 2 Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes

Background. Our aim was to evaluate the protective effect of lipoic acid (LA) on fetal outcome of diabetic mothers. Methods. Diabetes was induced in female rats using streptozotocin and rats were made pregnant. Pregnant control (group 1; = 9; and group 2; = 7) or pregnant diabetic (group 3; = 10; and group 4; = 8) rats were treated daily with either LA (groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the fetuses, placentas, and membranes were dissected, examined morphologically, and then homogenized, to measure cyclooxygenase (COX) activities and metabolisms of prostaglandin (PG) E 2 (PGEM) and PGF 2 (PGFM) levels. The level of total glutathione was measured in the maternal liver and plasma and in all fetuses. Results. Supplementation of diabetic rats with LA was found to significantly ( < 0.05) reduce resorption rates in diabetic rats and led to a significant ( < 0.05) increase in liver, plasma, and fetuses total glutathione from LA-TD rats as compared to those from V-TD. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas, and membranes were characteristic of experimental diabetic gestation associated with malformation. The levels of PGEM in malformed fetuses from LA-TD mothers was significantly ( < 0.05) higher than those in malformed fetuses from V-TD rats. Conclusions. LA treatment did not completely prevent the occurrence of malformations. Thus, other factors may be involved in the pathogenesis of the diabetesinduced congenital malformations

An adaptive delayed acknowledgment strategy to improve TCP performance in multi-hop wireless networks.

In multi-hop wireless networks, transmission control protocol (TCP) suffers from performance deterioration due to poor wireless channel characteristics. Earlier studies have shown that the small TCP acknowledgments consume as much wireless resources as the long TCP data packets. Moreover, generating an acknowledgment (ACK) for each incoming data packet reduces the performance of TCP. The main factor affecting TCP performance in multi-hop wireless networks is the contention and collision between ACK and data packets that share the same path. Thus, lowering the number of ACKs using the delayed acknowledgment option defined in IETF RFC 1122 will improve TCP performance. However, large cumulative ACKs will induce packet loss due to retransmission time-out at the sender side of TCP. Motivated by this understanding, we propose a new TCP receiver with an adaptive delayed ACK strategy to improve TCP performance in multi-hop wireless networks. Extensive simulations have been done to prove and evaluate our strategy over different topologies. The simulation results demonstrate that our strategy can improve TCP performance significantly

Spiro-cyklotrifosfazen z trzema funkcyjnymi grupami końcowymi: synteza i charakterystyka struktury nowych policyklotrifosfazenów z grupami zasad Schiffa

A new tris-spiro-(3,4-dioxybenzaldehyde)cyclotriphosphazene [PNCHO] was synthesized from the condensation of hexachlorocyclotriphosphazene with 3,4-dihydroxybenzaldehyde in the presence of strong base. Further reaction of the trialdehydic cyclotriphosphazene based molecules [PNCHO] with three different dianilines (benzidine, 4,4’-methylenedianiline and 4,4′-Sulfonyldianiline) resulted in creation of a new poly(tris-spiro-3,4-dioxbenzene)cyclotriphosphazenes with Schiff-base groups [PNSB1-3]. The structures of [PNCHO] and the polycyclotriphosphazenes-schiff base derivatives were characterized by means of FTIR, 1H, 13C NMR and C.H.N elemental analysis. Differential scanning calorimetery (DSC) revealed a relatively high glass transition temperature (135−175°C) of obtained polymers. Thermal gravimetric analysis (TGA) exhibited their good thermal stability (up to 375°C). The char yield was about 36–42% at 700°C. All polymers were self-extinguishable as the LOI (Limiting Oxygen Index) values were above 26% and this meets with the V-0 and V-1, classification (UL-94). No fumes, soot, or toxic gases emission were observed during burning. The polymers obtained can be used as environmentally friendly, flame-retardant materials.Nowy tris-spiro-(3,4-dioksybenzaldehydo)cyklotrifosfazen [PNCHO] zsyntetyzowano w procesie kondensacji heksachlorocyklotrifosfazenu z 3,4-dihydroksybenzaldehydem w obecności silnej zasady. W wyniku reakcji trialdehydo cyklotrifosfazenów z trzema różnymi dianilinami (benzydyna, 4,4’-metylenodianilina i 4,4’-sulfonylodianilina) otrzymano poli(tris-spiro-3,4-dioksabenzeno)cyklotrifosfazeny z zasadami Schiffa [PNSB1-3]. PNCHO i pochodne policyklotrifosfazen-zasady Schiffa scharakteryzowano za pomocą analizy elementarnej (C, H, N), FTIR, 1H, 13C NMR. Metodą różnicowej kalorymetrii skaningowej (DSC) wykazano wysoką temperaturę zeszklenia (135−175°C) otrzymanych polimerów. Metodą analizy termograwimetrycznej (TGA) potwierdzono ich dobrą stabilność termiczną (do 375°C). Stopień zwęglenia po spaleniu wynosił w temp. 700°C ok. 36–42%. Wszystkie polimery były samogasnące, ponieważ wartości LOI (Limiting Oxygen Index) przekraczały 26%, co odpowiada klasie palności V-0 i V-1 (UL-94). Podczas spalania nie zaobserwowano emisji oparów, sadzy ani toksycznych gazów. Otrzymane polimery mogą znaleźć zastosowanie jako przyjazne dla środowiska materiały trudnopalne

Synteza, charakterystyka, właściwości termiczne i ognioodporne nowych homokopolimerów i kopolimerów blokowych poliakrylanu i żywicy epoksydowej z rdzeniem cyklotrifosfazenowym

New homo- and block copolymers composed of polyacrylate and epoxy resin with hexafunctional cyclotriphosphazene core were synthesized and characterized by FT-IR and 1H-, 13C-, and 31P- NMR. The first homopolymer, PN-polyacry was prepared from the direct condensation of 2-hydroxyethylacrylate with acyl chloride of hexakis(4-carboxyphenoxy)cyclotriphosphazene, PN-acyl. The second homopolymer, PN-Ep, was prepared in a direct reaction of catalyzed carboxyl groups of hexakis(4-carboxyphenoxy)cyclotriphosphazene PN-COOH with epoxy resin via an oxirane ring opening reaction. The block copolymer, PN-Ep/polyacry, was prepared from the partial coupling of 2-hydroxyethyl acrylate with the PN-acyl, followed by the reaction of unreacted carboxyl groups with epoxy resin. Differential scanning calorimetry (DSC) analysis of the PN-Ep/polyacry copolymer exhibited good compatibility between polyacrylate and cured epoxy resin. Thermal gravimetric analysis (TGA) revealed that the prepared polymeric systems accumulate 30–38 wt % char at elevated temperatures, compared to neat polyacrylate and cured epoxy resin, which accumulate negligible char at 700 °C. The limiting oxygen index (LOI) exhibited significant enhancement of fire retardant properties of the prepared polymeric systems. A scanning electron microscopy (SEM) morphology study revealed that PN-polyacry and PN-Ep/polyacrylate produced intumescent char residues while PN-Ep produced solid dense char with a nonporous surface.Zsyntetyzowano nowe homopolimery i kopolimery blokowe złożone z poliakrylanu i żywicy epoksydowej z sześciofunkcyjnym rdzeniem cyklotrifosfazenu. Struktury scharakteryzowano metodami FT-IR i 1H-, 13C- oraz 31P-NMR. Pierwszy homopolimer, poliakrylan (PN), wytworzono w bezpośredniej kondensacji akrylanu 2-hydroksyetylu z chlorkiem acylu heksakis(4-karboksyfenoksy)cyklotrifosfazenu (PN-acyl). Drugi homopolimer (PN-Ep) wytworzono w katalizowanej bezpośredniej reakcji grup karboksylowych heksakis(4-karboksyfenoksy) cyklotrifosfazenu (PN-COOH) z żywicą epoksydową w wyniku otwarcia pierścienia oksiranowego. Kopolimer blokowy (PN-Ep/poliakry) otrzymano w procesie częściowego sprzęgania akrylanu 2-hydroksyetylu z PN-acylem i następnej reakcji nieprzereagowanych grup karboksylowych z żywicą epoksydową. Analiza kopolimeru PN-Ep/poliakry za pomocą różnicowego kalorymetru skaningowego (DSC) wykazała dobrą kompatybilność między poliakrylanem i utwardzoną żywicą epoksydową, a na podstawie analizy termograwimetrycznej (TGA) stwierdzono, że przygotowane układy polimerowe spalają się w podwyższonej temperaturze do karbonizatu (30—38% mas.), podczas gdy czysty poliakrylan i utwardzona żywica epoksydowa w 700 °C wytwarzają jego pomijalne ilości. Wartość granicznego wskaźnika tlenowego (LOI) wskazywała na znaczące zwiększenie ognioodporności przygotowanych układów polimerowych. Badanie morfologii przy użyciu skaningowego mikroskopu elektronowego (SEM) wykazało, że w wyniku spalania poliakrylanu PN i PN-Ep/poliakrylanu wytwarza się pozostałość pęczniejących karbonizatów, podczas gdy w procesie spalania PN-Ep wytwarzał się zwarty gęsty osad o nieporowatej powierzchni

Concentration dependent structural ordering of poloxamine 908 on polystyrene nanoparticles and their modulatory role on complement consumption

Adsorption of poloxamine 908, a tetrafunctional polyethylene oxide (PEO)-polypropylene oxide ethylenediamine block copolymer, onto the surface of monodispersed polystyrene nanoparticles (232±0.33 nm) follows a bimodal pattern. Initially, the isotherm follows a Langmuir profile with a plateau observable over a very narrow equilibrium poloxamine concentration (0.0018–0.0031 mM). The isotherm then begins to rise again, reaching a final plateau at equilibrium poloxamine concentrations above 0.0089 mM. Similarly, the profile of the adsorbed layer thickness of poloxamine on the surface of nanoparticles is bimodal. The first plateau corresponds to a thickness of 4.6±0.07 nm, which occurs over the same range of poloxamine concentrations as in the initial plateau of the adsorption isotherm. The second plateau corresponds to a thickness of 9.53±0.32nm, observable at a minimum poloxamine concentration of 0.0067 mM. By using a calculated radius of gyration of a PEO chain in poloxamine as 3.1 nm, these observations reflect dynamic changes in the arrangement of surface projected PEO chains; a mushroom-like conformation at the first plateau region of the adsorption isotherm, followed by a transition into a brush-like conformation. These conformational changes are also reflected in rheological studies; the apparent viscosity of nanoparticles in which the PEO chains are in mushroom conformation is considerably higher than particles displaying the brush conformation. Further, atomic force microscopy studies (height profile and phase lag measurements) corroborated that the proposed poloxamine concentration dependent transition of surface associated PEO chains from mushroom to brush appearance is conserved when nanoparticles are dried under ambient conditions. Finally, we compared the influence of the surface PEO characteristics on complement consumption in human serum. Our results show complement-activating nature of all poloxamine-coated nanoparticles. However, complement consumption is reduced substantially with particles bearing a minimum of 11448 poloxamine molecules on their surface, thus demonstrating the importance of PEO surface density as well as brush conformation in suppressing complement consumption. This relationship between surface characteristics of poloxamine nanoparticles and their in vivo performance is discussed

Transdermal patches: Design and current approaches to painless drug delivery

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation

Modification of the Stewart biphasic colorimetric assay for stable and accurate quantitatitive determination of Pluronic and Tetronic block copolymers for application in biological systems

Block copolymers are increasingly being applied in areas such as transfection, membrane sealing, site-specific targeting, and bionanoengineering yet there is a relative paucity of assays available for simple, stable and reproducible colorimetric determination of copolymer concentration in solution. We have focused on improving the accuracy and reproducibility of a modified version of the Stewart biphasic colorimetric assay for quantitative determination of Pluronic (poloxamer) and Tetronic (poloxamine) macromolecules. The optimized assay achieved linear response ranges in chloroform for commonly used copolymers such as poloxamine 904 (20–300 μg/ml), poloxamine 908 (10–400 μg/ml), poloxamer 402 (20–400 μg/ml), and poloxamer 407 (10–400 μg/ml). Variation in the type of chlorinated solvent used significantly increased assay sensitivity, presumably through macromolecular reorientation, affording increased access for copolymer–ferrothiocyanate complexation. This was found to be optimally favored by the planar geometry of the solvent cis 1,2-dichloroethylene. For application to biological systems copolymer–protein interactions were for the first time determined and were found to be dependent on the fraction of hydrophobic constituents of the block copolymers and protein type. For instance serum albumin was found to interact with copolymers of low hydrophilic–lipophilic balance values and poly(propylene oxide) contaminants, whereas this interaction was not significant with the relatively hydrophilic IgG. In such systems the colorimetric assay directly determines the fraction of unbound (free) copolymer in the presence of proteins