Synthesis, swelling and drug release behavior of poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) hydrogel

In this study, poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) (poly(DEA-co-NHMAA)) hydrogels were synthesized by changing the initial DEA/NHMAA mole ratio, N,N'-methylenebisacrylamide and total monomer concentration. The thermosensitive and mechanical performances were optimized by altering the above parameters. The hydrogels were characterized by using Fourier transform infrared (FTIR) spectroscope and scanning electron microscope (SEM). In comparison with the PDEA hydrogel, the equilibrium swelling ratio (ESR) and lower critical solution temperature (LCST) of the hydrogels increased with the increase of NHMAA content in the feed. The swelling kinetics was also studied. The release behaviors of the model drug, aminophylline, are found dependent on hydrogel composition and environmental temperature, which suggests that these materials have potential application as intelligent drug carriers.     

The synthesis,swelling behaviour and rheological properties of chemically crosslinked thermosensitive copolymers based on <Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide

In this contribution thermosensitive polymer matrices based on N-isopropylacrylamide have been developed. The hydrogels were prepared by photopolymerisation of N-isopropylacrylamide and 1-vinyl-2-pyrrolidinone in appropriate amounts of distilled water. The monomers were cured using a UV-light sensitive initiator called 1-hydroxycyclohexylphenylketone. These copolymers were crosslinked using ethylene glycol dimethacrylate and poly(ethylene glycol) dimethacrylate with molecular weights 600 and 1,000, at 0.1 wt% of the total monomer content. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR) and the transition temperature of the hydrogels was determined using modulated differential scanning calorimetry (MDSC). By altering the feed ratio, hydrogels were synthesised to have lower critical solution temperatures (LCST) around 37 °C. This ability to shift the phase transition temperature of the gels provides excellent flexibility in tailoring transitions for specific uses. The samples synthesised with PEG1000DMA crosslinking agents absorbed over 18 times their weight in water, while maintaining good gel integrity thus falling marginally short of being characterised as superabsorbent. Each of the samples showed similar deswelling behaviour at 37 °C. Rheological studies showed that increasing the molecular weight of the crosslinking agent caused an increase in hydrogel strength.     

In vitro release profile of anti-ulcer drug rabeprazole from biocompatible psyllium-PVA hydrogels

The present article discusses the synthesis, characterization and haemocompatibility behaviour of the psyllium-PVA hydrogels prepared by chemical method in the presence of N,N′-methylenebisacrylamide. These hydrogels have been characterized by Fourier Transform infrared spectroscopy, thermo gravimetric analysis, swelling and drug release studies. The release of model drug rabeprazole sodium from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism. Psyllium itself acts as anti-ulcer agent and release of rabeprazole from the drug loaded hydrogels may enhance the curing potential of the drug delivery device. The haemocompatibility was evaluated by studying the blood interactions with hydrogels with reference to thrombogenicity and haemolytic potential. Thrombogenicity results indicate that hydrogels are non-thrombogenic as the weight of clot formed and thrombus percentage for hydrogels was less than the positive control. The haemolytic index has been observed <5%. These observations indicate that these hydrogels are haemo-compatible and hence could be used for oral administration of antiulcer drugs.     

The effect of salts and pH buffered solutions on the phase transition temperature and swelling of thermoresponsive pseudogels based on <Emphasis Type="Italic">N-</Emphasis>isopropylacrylamide

The temperature sensitive nature of poly(N-isopropylacrylamide) makes it an attractive candidate for controlled drug delivery devices. A series of temperature responsive poly (N-isopropylacrylamide)-polyvinyl pyrrolidinone random copolymers were produced by free radical polymerisation using 1-hydroxycyclohexylphenyketone as a UV-light sensitive initiator. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR). The copolymers possess a lower critical solution temperature (LCST) in pure water, but the transition temperature may be affected by the addition of various cosolutes. The LCST of the pseudogels (physically crosslinked gels) was investigated in distilled water and a variety of salt and pH buffer solutions, using modulated differential scanning calorimetry (MDSC) and rheological analysis. The pH buffer solutions prepared mimic the variety of conditions encountered by drug delivery systems administered orally. The pH effects on the LCSTs of the temperature sensitive gels appear not obvious; while the salts used to prepare the pH buffer solutions have a more notable effect (‘salting out effect’) on the phase transition temperature. All swelling studies were carried out on the hydrogels at 37°C in distilled water, pH buffer 1.2 and pH buffer 6.8. The swelling/dissociation behaviour of the gels is found to be highly dependent on the pH buffer solution used, as the salts incorporated in preparing the pH buffer solutions lowers the phase transition of the copolymers to below the test temperature of 37°C, thus making them less soluble.     

Poly (vinyl alcohol)/poly (acrylamide‐ co ‐diallyldimethyl ammonium chloride) semi‐IPN hydrogels for ciprofloxacin hydrochloride drug delivery

Herein, the authors developed a new and potential semi‐interpenetrating polymer network (semi‐IPN) hydrogels of poly vinyl alcohol (PVA), acryl amide and diallyldimethyl ammonium chloride employing chemical cross‐linker N, N''‐methylene bisacrylamide (NNMBA) and ammonium persulphate as an initiator by radical polymerisation. To analyse the copolymer formation between two monomers and IPN cross‐linking reaction, the resulting hydrogel was characterised by Fourier transform infrared spectroscopy and the surface morphology was analysed using scanning electron microscopy. Differential scanning calorimetry and X‐ray diffraction studies were also carried out for investigating drug loading and distribution and swelling experiments were carried out for the uptake of water. In vitro release of ciprofloxacin hydrochloride from hydrogel was performed at intestinal conditions. The amount of PVA, NNMBA and total monomer concentration was found to strongly control the drug release behaviour from the hydrogels.Inspec keywords: hydrogels, polymer blends, biomedical materials, drug delivery systems, polymerisation, Fourier transform infrared spectra, surface morphology, scanning electron microscopy, differential scanning calorimetry, X‐ray diffraction, swelling, biological organs, ammonium compoundsOther keywords: PVA‐poly(acrylamide‐co‐diallyldimethyl ammonium chloride) semiIPN hydrogels, ciprofloxacin hydrochloride drug delivery, semiinterpenetrating polymer network hydrogels, polyvinyl alcohol, acryl amide, diallyldimethyl ammonium chloride, chemical crosslinker N,N''‐methylene bisacrylamide, ammonium persulphate, radical polymerisation initiator, NNMBA, copolymer formation, IPN crosslinking reaction, Fourier transform infrared spectroscopy, surface morphology, scanning electron microscopy, differential scanning calorimetry, X‐ray diffraction, drug loading, drug distribution, swelling, water uptake, in vitro ciprofloxacin hydrochloride release, intestinal conditions, total monomer concentration, drug release behaviour     

Thermosensitive behavior in cell culture media and cytocompatibility of a novel copolymer: poly(N-isopropylacrylamide-co-butylacrylate)

Cell sheet technology is a promising step forward in tissue engineering. Cell sheets are usually generated using Poly(N-isopropylacrylamide) hydrogels due to their swelling change around the lower critical solution temperature (LCST). Nevertheless, LCST can be affected by cell culture medium components and therefore it is necessary to ensure that the polymer preserves its thermosensitivity under these conditions. We propose a novel thermosensitive crosslinked-copolymer: Poly(N-isopropylacrylamide-co-butylacrylate). This copolymer is shown to be cytocompatible and thermosensitive under cell culture medium conditions, and besides, it can be synthesized inexpensively. Thermosensitivity was investigated by determining the LCST with differential scanning calorimetry and swelling/ratio measurements. Cytocompatibility and capacity to deliver cell sheets were studied employing 3T3 and human oral epithelial cells. In conclusion, we obtained a thermosensitive copolymer that allows cell sheet formation/detachment by using a simple and low-cost polymerization method. Furthermore, crosslinking allows easy manipulation of cell sheets growing on the copolymer for potential in situ applications.     

Synthesis and characterization of a thermo-sensitive poly(N-methyl acryloylglycine methyl ester) used as a drug release carrier

In this article, poly(N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by ¹H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers (N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.     

Swelling and diffusion characteristics of modified poly (N-isopropylacrylamide) hydrogels

Thermo-responsive hydrogels are capable of swelling changes to external temperature. A series of modified poly (N-isopropylacrylamide) (PNIPA) hydrogels was synthesized by free radical polymerization in aqueous solution. Acrylamide (AAm) was used to increase the lower critical solution temperature (LCST), while sodium alginate (SA) was used to improve the swelling performance of the hydrogels. Experiments show that 5.5% mass ratio of AAm increased the LCST by about 9 °C above that of conventional PNIPA. Also, SA significantly improved the equilibrium swelling ratio associate with temperature change. Trypan blue diffusion revealed significant differences in the fluid release obtained from hydrogels with modified LCST and swelling properties. The implications of the modified fluid release and swelling characteristics are also discussed for the device design of thermo-sensitive hydrogels for localized drug delivery.     

Release of BSA from porous matrices constituted of alginate–Ca and PNIPAAm-interpenetrated networks

The synthesis of thermosensitive Interpenetrating Polymer Network (IPN) hydrogels and the release of Bovine Serum Albumin (BSA) from the hydrogels were reported. The hydrogels, constituted of poly(N-isopropyl acrylamide) PNIPAAm network interpenetrated in alginate–Ca²⁺ network, were synthesized in a two-stepped process. In the first step, PNIPAAm network was synthesized from an aqueous solution containing N-isopropyl acrylamide (NIPAAm) monomers and N,N′-methylene-bis-acrylamide (MBAAm) co-monomers, and sodium alginate (SA) (1 or 2% w/v). The concentration of NIPAAm monomers in the hydrogel-forming solution was always 2.5, 5.0 or 10.0% (w/v). In the second step, alginate–Ca²⁺ networks were formed by immersion of the membrane, obtained on the first step, in a 1.0% (w/v) aqueous calcium chloride. The IPN hydrogels were characterized as a function of temperature (from 25 to 45 °C) through the following measurements: drop water contact angle (DWCA), compression elastic modulus (E) and cross-linking density (ν_e). The morphology was investigated using scanning electronic microscopy (SEM). In vitro release of BSA from the hydrogels was monitored by UV–Vis spectroscopy at 22 °C and 37 °C. DWCA results showed a decrease in the hydrogel hydrophilicity when the temperature and/or the PNIPAAm amount on hydrogels were increased. PNIPAAm-loader hydrogels are more compacted and presented elevated rigidity, mainly above 35 °C. This trend was attributed to the collapsing of PNIPAAm chains as the hydrogels were warmed above its Lower Critical Solution Temperature (LCST), which in aqueous solution is ca. 32–33 °C. The amount of BSA released from the alginate–Ca²⁺/PNIPAAm hydrogels changes inversely to both amount of PNIPAAm and temperature. The transport of BSA from the hydrogels was evaluated through a conventional model. In the lesser-compacted hydrogels the release occurs mostly by diffusion. In the more compacted ones the chain relaxation contributes to the BSA release. Thus, the alginate–Ca²⁺/PNIPAAm IPN-typed matrixes may be considered as smart hydrogels for the release of BSA, because the amount and rate of BSA released may be tailored by both the NIPAAm concentration in the hydrogel-forming solution and the control of temperature of hydrogel.     

Synthesis and characterization of a thermo-sensitive poly(<Emphasis Type="Italic">N</Emphasis>-methyl acryloylglycine methyl ester) used as a drug release carrier

In this article, poly(N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by ¹H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers (N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.     

Photopolymerisation and characterisation of negative temperature sensitive hydrogels based on N,N-diethylacrylamide

Despite the many advantages of photopolymerisation in the fabrication of hydrogels, studies on the synthesis of poly(N,N-diethylacrylamide) (PDEAAm) using this technique have received limited attention in the literature. A series of temperature sensitive hydrogels were prepared by free-radical crosslinking copolymerisation of N,N-diethylacrylamide (DEAAm) with 1-vinyl-2-pyrrolidinone (NVP) and N,N-dimethylacrylamide (DMAAm), respectively. Two ultraviolet (UV) light sensitive initiators were trialled in the synthesis, namely 1-hydroxycyclohexylphenylketone and 2-hydroxy-1-[4-(hydroxy-ethoxy)phenyl]-2-methyl-1-propanone, with poly(ethylene glycol)dimethacrylate being used as the crosslinking agent. The lower critical solution temperatures (LCSTs) of the hydrogels synthesised were shown to be close to body temperature using cloud point measurement and modulated differential scanning calorimetry, which is favourable particularly for ‘smart’ drug delivery applications. The swelling behaviour of the samples was investigated upon stepwise temperature change revealing that the hydrogels underwent reproducible pulsatile swelling behaviour. Oscillatory rheological studies showed that increasing the ratio of crosslinking agent could be used as a means of improving the mechanical properties of the photopolymerised temperature sensitive hydrogels.     

Slow release of ciprofloxacin from double potential drug delivery system

Psyllium polysaccharide is a bulk laxative and has been used for the treatment of constipation which is responsible for the diverticulitis. Ciprofloxacin is an antibiotic used for the microorganism infested in the diverticula. Hence, the functionalization of psyllium with polyvinyl alcohol (PVA) and poly(acrylamide) [poly(AAm)] will develop the drug delivery system (DDS) with potential for dual action for the treatment of diverticulitis, that is, by treating the constipation due to laxative action of psyllium and release of ciprofloxacin from DDS in controlled manner. The optimum conditions for the synthesis of hydrogels have been obtained as 42.21 × 10⁻² mol/L of AAm, 3% (w/v) of PVA, 32.43 × 10⁻³ mol/L of N,N′-methylenebisacrylamide (NN-MBA), 17.53 × 10⁻³ mol/L ammonium persulfate, and 1 g of psyllium. The characterization of the hydrogels has been carried out by SEMs, EDAX, FTIR, and swelling studies. Swelling and drug release studies have also been carried out to determine the mechanism of swelling of hydrogels and drug release from the drug loaded hydrogels. The release of the drug from the hydrogels occurred through Fickian diffusion mechanism in pH 2.2 and pH 7.4 buffer.     

Preparation and characterization of amidated pectin based hydrogels for drug delivery system

In the current studies attempts were made to prepare hydrogels by chemical modification of pectin with ethanolamine (EA) in different proportions. Chemically modified pectin products were crosslinked with glutaraldehyde reagent for preparing hydrogels. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), organic elemental analysis, X-ray diffraction studies (XRD), swelling studies, biocompatibility and hemocompatibility studies. Mechanical properties of the prepared hydrogels were evaluated by tensile test. The hydrogels were loaded with salicylic acid (used as a model drug) and drug release studies were done in a modified Franz’s diffusion cell. FTIR spectroscopy indicated the presence of primary and secondary amide absorption bands. XRD studies indicated increase in crystallinity in the hydrogels as compared to unmodified pectin. The degree of amidation (D _A) and molar and mass reaction yields (Y _M and Y _N) was calculated based on the results of organic elemental analysis. The hydrogels showed good water holding properties and were found to be compatible with B-16 melanoma cells & human blood.     

pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release

Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as “smart” polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37°C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37°C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B₁₂ (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B₁₂ was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B₁₂ was investigated as a function of temperature, pH, and the CAB/SP ratio.     

Preparation,properties, and drug release of thermo- and pH-sensitive poly((2-dimethylamino)ethyl methacrylate)/poly(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethylacrylamide) semi-IPN hydrogels

In this paper, a series of semi-interpenetrating polymer network (semi-IPN) hydrogels based on poly((2-dimethylamino)ethyl methacrylate)/poly (N,N-diethylacrylamide) (PDMAEMA/PDEA) were synthesized by changing the initial PDMAEMA/DEA molar ratio at room temperature. The influence of this additive on the property of resulting PDEA hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that the semi-IPN hydrogels have interconnected porous network structures. The glass transition temperature (T _g) of the semi-IPN hydrogels was observed by differential scanning calorimetry (DSC). Equilibrium swelling ratio (ESR), swelling and deswelling dynamics of the hydrogels responding to temperature and pH were investigated in detail. Compared to PDEA, the semi-IPN hydrogels exhibited excellent mutative values in response to an alternation of the temperature and pH, and showed fast swelling and deswelling rates in response to temperature and pH change. The release behaviors of the model drug, aminophylline, were found dependent on hydrogel compositions and environmental temperature. These results suggest that the stimuli semi-IPN hydrogel have potential application as intelligent drug carriers.     

Stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels for oral controlled release drug delivery

This study evaluated the potential of stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels as oral controlled-release drug delivery carriers. Hydrogels were synthesized by graft copolymerization of the monomers onto bacterial cellulose (BC) fibers by using a microwave irradiation technique. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). FT-IR spectroscopy confirmed the grafting. XRD showed that the crystallinity of BC was reduced by grafting, whereas an increase in the thermal stability profile was observed in TGA. SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading. The hydrogels demonstrated a pH-responsive swelling behavior, with decreased swelling in acidic media, which increased with increase in pH of the media, reaching maximum swelling at pH 7. The release profile of the hydrogels was investigated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The hydrogels showed lesser release in SGF than in SIF, suggesting that hydrogels may be suitable drug carriers for oral controlled release of drug delivery in the lower gastrointestinal tract.     

Swelling behavior and drug release of NIPAAm/PEGMEA copolymeric hydrogels with different crosslinkers

Poly(ethylene glycol) methylether acrylate (PEGMEA) and tetraethylene glycol diacrylate (TEGDA) were first synthesized. The thermosensitive hydrogels were then prepared from N-isopropylacrylamide (NIPAAm), PEGMEA, and three crosslinkers with different structures such as N, N′-methylene-bis-acrylamide (NMBA), TEGDA, and poly(ethylene glycol) dimethacrylate (EGDMA). The influence of polymerization factors such as the kind and amount of crosslinker and initial total monomer concentration on the swelling behavior, gel strength, effective crosslinking densities, and number-average molecular weight between crosslink points ( ) for the present copolymeric hydrogels was investigated. The results indicate that the swelling ratios for the present copolymeric gels decrease with increase in temperature. In addition, the results also showed that the higher swelling ratios for the present gels prepared from TEGDA were obtained due to the larger space between the gel networks. The crosslinking density depends on the swelling ratio and the kind and extent of crosslinker. In addition, the drug release behavior for the present copolymeric gels was investigated.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

A smart hydrogel-based time bomb triggers drug release mediated by pH-jump reaction

Abstract

We demonstrate a timed explosive drug release from smart pH-responsive hydrogels by utilizing a phototriggered spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (o-NBA) was integrated into poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels. o-NBA-hydrogels demonstrated the rapid release of protons upon UV irradiation, allowing the pH inside the gel to decrease to below the pK_a value of P(NIPAAm-co-CIPAAm). The generated protons diffused gradually toward the non-illuminated area, and the diffusion kinetics could be controlled by adjusting the UV irradiation time and intensity. After irradiation, we observed the enhanced release of entrapped L-3,4-dihydroxyphenylalanine (DOPA) from the gels, which was driven by the dissociation of DOPA from CIPAAm. Local UV irradiation also triggered the release of DOPA from the non-illuminated area in the gel via the diffusion of protons. Conventional systems can activate only the illuminated region, and their response is discontinuous when the light is turned off. The ability of the proposed pH-jump system to permit gradual activation via proton diffusion may be beneficial for the design of predictive and programmable devices for drug delivery.     

Phospholipid–polymer hybrid nanoparticle-mediated transfollicular delivery of quercetin: prospective implement for the treatment of androgenic alopecia

Abstract

Objectives: The aim of the study was to deliver effective doses of quercetin (Que) to the lower region of hair follicles (HFs) using the transfollicular route through dipalmotylphosphatidylcholine (DPPC)-reinforced poly lactide-co- glycolide nanoparticles (DPPC-PLGA hybrid NPs) for the treatment of alopecia.

Method: PLGA and DPPC-PLGA hybrid NPs were prepared by double-emulsification solvent evaporation method. NPs were characterized for size, shape, zeta potential entrapment and drug release. Drug-polymer interactions were determined by infrared spectroscopy (Fourier transform infrared spectroscopy, FTIR) and differential scanning calorimetry (DSC). Follicular uptake of fluorescent marker tagged NPs was assessed on isolated rat skin by fluorescent microscopy. Potential of hybrid NPs to induce hair regrowth was tested on testosterone-induced alopecia in rat models by visual inspection, hair follicular density measurement (no./mm), and histological skin tissue section studies.

Key findings: Hybrid NPs had mean vesicles size 339?±?1.6, zeta potential –32.6?±?0.51, and entrapment efficiency 78?±?5.5. Cumulative drug release after 12?h was found to be 47.27?±?0.79%. FTIR and DSC confirmed that drug was independently dispersed in the amorphous form in the polymer. Data from fluorescence microscopy suggested that NPs were actively taken up by HFs. In-vivo studies on alopecia-induced rat models showed that hybrid NPs improved hair regrowth potential of Que and accumulation of NPs at HFs end region inhibit HFs cells apoptosis.

Conclusion: This study concludes that phospholipid–polymer hybrid NPs could be the promising transfollicular delivery system for Que in the treatment of androgenic alopecia management.