Emergency contraceptive use of Metronidazole among University female students in Dodoma region of Tanzania: a descriptive cross-sectional study.

BACKGROUND: Metronidazole is known for its therapeutic effect as antibacterial and anti-parasitic. However, its toxicity on the reproductive system remains unclear. Metronidazole use in rodents is associates with toxic effects on the reproductive system, including hormonal alterations, reduced number of fertile cells and reduced sites for implantation, size of the placental disc area, constituent elements of the labyrinth, and spongiotrophoblast layers. Its use at a therapeutic dose among humans has been associated with an increased risk of spontaneous abortion. The effects on the reproductive system in humans may result in misconceptions about contraceptive effects hence sexually active individuals like students who, for any reason, fail to access safe contraceptive services use any possible methods to protect them from conception. This study aims to investigate the unofficial (un-prescribed) use of Metronidazole as an emergency contraceptive and some of its associated factors. METHODS: This quantitative cross-sectional study involved 470 participants where stratified random sampling technique was used to obtain the sample from three educational institutions in the Dodoma Municipal, Dodoma region. Collected data were analyzed using SPSS version 25, descriptive statistical analysis was done to determine frequencies, percentages, and association, p < 0.05 was used to determine statistical significance. Further analysis using Multivariate binary logistic regression was done to determine the nature of the association between the study variables. RESULTS: The finding shows that 169(62.4%) use Metronidazole as an emergency contraceptive. Notably, 345(73.4%) stated that they had ever heard someone use Metronidazole for contraception, especially their peers. Furthermore, an increase in the year of study was significantly associated with reduced use of Metronidazole as an emergency contraceptive (B = [-0.45], p = [0.02]). Furthermore, an increase in age, studying in non-medical college/university, the experience of using contraceptive methods, and hearing someone ever used Metronidazole was found to be positively associated with its use as an emergency contraceptive, although not statistically significant. CONCLUSION: Metronidazole was found to be used as an emergency contraceptive in high doses, different factors associated with its use, and reasons influencing its use. Further research may be done to explore the toxicological effect of high doses of Metronidazole as a contraception and compare the efficiency of Metronidazole over other emergency contraceptives.

Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vancomycin.

Stimuli-responsive nano-drug delivery systems can optimize antibiotic delivery to infection sites. Identifying novel lipids for pH responsive delivery to acidic conditions of infection sites will enhance the performance of nano-drug delivery systems. The aim of the present investigation was to synthesize and characterize a biosafe novel pH-responsive lipid for vancomycin delivery to acidic conditions of infection sites. A pH-responsive solid lipid, N-(2-morpholinoethyl) oleamide (NMEO) was synthesized and used to prepare vancomycin (VCM)-loaded solid lipid nanoparticles (VCM_NMEO SLNs). The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and entrapment efficiency (EE) of the formulation were 302.8 ±â€¯0.12 nm, 0.23 ±â€¯0.03, -6.27 ±â€¯0.017 mV and 81.18 ±â€¯0.57% respectively. The study revealed that drug release and antibacterial activity were significantly greater at pH 6.0 than at pH 7.4, while the in silico studies exposed the molecular mechanisms for improved stability and drug release. Moreover, the reduction of MRSA load was 4.14 times greater (p < 0.05) in the skin of VCM_NMEO SLNs treated mice than that of bare VCM treated specimens. Thus, this study confirmed that NMEO can successfully be used to formulate pH-responsive SLNs with potential to enhance the treatment of bacterial infections.

Pegylated oleic acid: A promising amphiphilic polymer for nano-antibiotic delivery.

Vancomycin (VM), a last resort to control methicillin-resistant S. aureus (MRSA) infections, is on the verge of becoming ineffective. Novel nano delivery systems of VM have the potential to combat MRSA. The search for novel materials for nanoantibiotic development is therefore an active research area. In this study, oleic acid (OA) was coupled with monomethoxy polyethylene glycol (mPEG) to obtain a novel bio-safe amphiphilic polymer, mPEG-OA. The critical micelle concentration of mPEG-OA, was found to be 4.5×10-8m/L. VM-loaded polymersomes were prepared from mPEG-OA and evaluated for size, polydispersity index (PDI), zeta potential (ZP), surface morphology, drug release, in vitro and in vivo antibacterial activity. The size, PDI and ZP of VM-loaded polymersomes were 142.9±7.5nm, 0.228±0.03 and -18.3±3.55mV respectively. Transmission electron microscopy images revealed the spherical shape of polymersomes. The encapsulation efficiency was 53.64±1.86%. The drug release from polymersomes was sustained and in vitro antibacterial activity was 42- and 5-fold more against S. aureus and MRSA, compared with plain VM. An in vivo BALB/c mice, skin infection models revealed that treatment with VM-loaded polymersomes significantly reduced the MRSA burden compared with plain VM and blank polymersomes. There was a 183 and a 25-fold reduction in the MRSA colony finding units load in mice skin treated with VM-loaded polymersomes compared to that treated with blank polymersomes and bare VM respectively. In summary, the developed VM-loaded polymersomes from novel mPEG-OA polymer were found to be a promising nanoantibiotic against MRSA.

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.

CONTEXT AND OBJECTIVE: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. MATERIALS AND METHODS: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. RESULTS AND DISCUSSION: There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. CONCLUSION: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.

A review of integrating electroactive polymers as responsive systems for specialized drug delivery applications.

Electroactive polymers (EAPs) are promising candidate materials for the design of drug delivery technologies, especially in conditions where an "on-off" drug release mechanism is required. To achieve this, EAPs such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be blended into responsive hydrogels in conjunction with the desired drug to obtain a patient-controlled drug release system. The "on-off" drug release mechanism can be achieved through the environmental-responsive nature of the interpenetrating hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules; (ii) conformational changes that occur during redox switching of EAPs; or (iii) electroerosion. These release mechanisms are not exhaustive and new release mechanisms are still under investigation. Therefore, this review seeks to provide a concise incursion and critical overview of EAPs and responsive hydrogels as a strategy for advanced drug delivery, for example, controlled release of neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine delivery. The review further discusses techniques such as linear sweep voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry for the determination of the redox capability of EAPs. The future implications of the hydrogel-EAP composites include, but not limited to, application toward biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors and may be utilized to their full potential in the form of injectable devices as nanorobots or nanobiosensors.

A novel multilayered multidisk oral tablet for chronotherapeutic drug delivery.

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery.

Exploration of the biomacromolecular interactions of an interpenetrating proteo-saccharide hydrogel network at the mucosal interface.

The relationship between mucin (MUC) and pectin (PEC) was explored in an attempt to understand the biomacromolecular interactions that occur at mucosal surfaces when mucus membranes are exposed to PEC-based materials. These interactions were explored through techniques, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, SEM imagery of lyophilized MUC-PEC blends, thermodynamic analysis, rheology investigations, and in silico static lattice atomistic simulations using a molecular mechanics energy relationships (MMER) approach. Three types of PEC that had different degrees of esterification and degrees of amidation were investigated at different MUC-PEC mass ratios (1:0, 1:1, 1:4, 1:9, and 0:1). The effect PEG 400 and Ca(2 +) in the MUC-PEC interactions were also studied. ATR-FTIR spectroscopy revealed broadening and strengthening of FTIR peaks at 3363 cm(-1) and between 3000-3650 cm(-1) due to stretching vibrations of the -OH, -COOH groups on MUC and PEC as well as the -N-H group on MUC. This suggested significant intra- and inter-molecular H-bonding. Morphologically, MUC-rich scaffolds were porous, thin, and multidirectional compared with the smooth, rigid, and unidirectional PEC-rich scaffolds. The Flory-Huggins interaction parameter (χ12 ) for all MUC-PEC mass ratios was negative, thus confirming MUC-PEC miscibility and interactions. UV absorbance increased with increasing relative concentration of PEC in the aqueous MUC-PEC dispersions. Furthermore, rheology investigations demonstrated synergistic enhancement in viscosity (η) and dynamic moduli upon the addition of PEG 400 and Ca(2 +) . MMER analysis revealed several key MUC-PEC interactions that corroborated well with the experimental data. Notably, higher esterification and larger mass ratios of PEC yielded greater MUC-PEC interactions.

Integration of biosensors and drug delivery technologies for early detection and chronic management of illness.

Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness.

A review of polymeric refabrication techniques to modify polymer properties for biomedical and drug delivery applications.

Polymers are extensively used in the pharmaceutical and medical field because of their unique and phenomenal properties that they display. They are capable of demonstrating drug delivery properties that are smart and novel, such properties that are not achievable by employing the conventional excipients. Appropriately, polymeric refabrication remains at the forefront of process technology development in an endeavor to produce more useful pharmaceutical and medical products because of the multitudes of smart properties that can be attained through the alteration of polymers. Small alterations to a polymer by either addition, subtraction, self-reaction, or cross reaction with other entities have the capability of generating polymers with properties that are at the level to enable the creation of novel pharmaceutical and medical products. Properties such as stimuli-responsiveness, site targeting, and chronotherapeutics are no longer figures of imaginations but have become a reality through utilizing processes of polymer refabrication. This article has sought to review the different techniques that have been employed in polymeric refabrication to produce superior products in the pharmaceutical and medical disciplines. Techniques such as grafting, blending, interpenetrating polymers networks, and synthesis of polymer complexes will be viewed from a pharmaceutical and medical perspective along with their synthetic process required to attain these products. In addition to this, each process will be evaluated according to its salient features, impeding features, and the role they play in improving current medical devices and procedures.

Design of an interpolyelectrolyte gastroretentive matrix for the site-specific zero-order delivery of levodopa in Parkinson's disease.

This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson's disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34-39 N/mm) and matrix resilience (44-47%) when different normality's of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm(3) and swellability values of 177-234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery.

Ligand-functionalized nanoliposomes for targeted delivery of galantamine.

The purpose of this study was to design ligand-functionalized nanoliposomes that are proficient in providing effective intracellular delivery of an alkaloid drug (galantamine) into PC12 neuronal cells in response to managing Alzheimer's disease (AD). Ligand-functionalized nanoliposomes were produced and validated for their physicochemical properties, in silico molecular mechanics energy relationships, ex vivo cytotoxicity, peptide coupling efficiency (PCE), drug entrapment efficiency (DEE), drug release, fluorometry and confocal microscopy. Particle sizes of the nanoliposomes ranged from 127 nm to 165 nm (PdI=0.39-0.03), zeta potential values of -18 mV to -36 mV, PCE from 40% to 78% while DEE ranged from 42% to 79%. The surface morphology of the nanoliposomes was stable, spherically and uniform in shape. Thermal behavior and Fourier transform infrared (FTIR) analyses confirmed that galantamine and the peptide-ligand were incorporated into the inner core and surface of the nanoliposomes, respectively. The optimized formulation showed sustained drug release (30% of drug released within 48 h). Fluorometry and confocal microscopy revealed that the ligand-functionalized nanoliposomes facilitated galantamine uptake into PC12 neuronal cells via the Serpin Enzyme Complex Receptor in a mediated manner. CytoTox-Glo™ cytotoxicity assay established the low cytotoxicity on PC12 neuronal cells when exposed to native nanoliposomes and the ligand-functionalized nanoliposomes. Response surface analysis demonstrated there was a high degree of correlation between the experimental and fitted values. Furthermore, ex vivo studies showed that the high galantamine accumulation into PC12 neuronal cells was influenced by the post-engineering of peptides on the surface of the galantamine-loaded nanoliposomes. MMER analysis aptly corroborated the experimental findings.

A novel stimuli-synchronized alloy-treated matrix for space-defined gastrointestinal delivery of mesalamine in the Large White pig model.

The study focussed on designing a Stimuli-Synchronized Matrix (SSM) for space-defined colonic delivery of the anti-inflammatory drug mesalamine. The configured matrix provided time-independent delivery and stimuli targeting. Formulations were optimized according to a Box-Behnken experimental design that constituted mesalamine-loaded BaSO4-crosslinked chitosan dispersed within a pectin, carboxymethylcellulose and xanthan gum complex. The complex was compressed into matrices and subsequently alloy-treated with pectin and ethylcellulose. In vitro drug release was determined in the presence and absence of colonic enzymes and the mean dissolution time was used for formulation optimization. To mechanistically elucidate the synchronous catalytic action of the enzymes pectinase and glucosidase on the matrix, computer-aided 3D modelling of active fractions of the enzyme-substrate complexes was generated to predict the orientation of residues affecting the substrate domain. Drug release profiles revealed distinct colonic enzyme responsiveness with fractions of 0.402 and 0.152 of mesalamine released in the presence and absence of enzymes, respectively after 24h. The commercial comparator product showed irreproducible release profiles over the same period (SD=0.550) compared to the SSM formulation (SD=0.037). FTIR spectra of alloy-treated matrices showed no peaks from 1589 to 1512cm(-1) after colonic enzyme exposure. With increasing enzyme exposure there were also no peaks between 1646 and 1132cm(-1). This indicated polymeric enzyme cleavage for controlled and space-defined release of mesalamine. Plasma concentration profiles in the Large White pig model produced a Cmax of 3.77±1.375µg/mL compared to 10.604±2.846µg/mL for the comparator formulation. The SSM formulation proved superior over the comparator product by providing superiorly controlled enzyme-responsive colonic drug delivery.

A novel pH-dependant and double crosslinked polymethacrylate-based polysphere matrix for enteric delivery of isoniazid.

This study aimed at developing double crosslinked isoniazid (INH)-loaded polymethyl-methacrylate-ethylcellulose (PMMA-EC) polyspheres for rate-controlled enteric drug delivery. A PMMA solution was manipulated with the addition of EC to produce polyspheres by drop-wise extrusion into a primary crosslinking solution of AlCl3 (25% w/v), before adding a second crosslinking solution of either 30% w/v BaCl2 (polysphere Batch A) or 30% w/v MgCl2 (polysphere Batch B). The polyspheres were then subjected to FTIR spectroscopic analysis, in vitro drug release studies, drug entrapment efficiency (DEE) determination as well as surface area and porositometric investigations. Molecular Mechanics (MM) simulations elucidated the interaction between the cations and the PMMA-EC combination. FTIR spectra revealed an affinity of PMMA for Ba(2+), Mg(2+) and Al(3+). SEM showed smooth robust polyspheres ranging between 4-6 mm. Porositometric analysis established that polysphere Batch A had larger pores (315.314 Åabs) than Batch B (234.603 Åabs). Drug release profiles from polysphere Batch A displayed burst release with 50% INH released within 2 h (N = 3) that was attributable to the larger ionic radius of the second crosslinker Ba(2+) compared Mg(2+) which was employed for polysphere Batch B. The latter produced polyspheres with superior control in INH release (<25% within 2 h) (N = 3) and a higher DEE with minimal pore formation. The experimental findings were well corroborated by the MM simulations.

Flavonoids and polymer derivatives as CYP3A4 inhibitors for improved oral drug bioavailability.

Molecular modeling computations were utilized to generate pharmaceutical grade CYP3A4-enzyme inhibitors. In vitro metabolism of felodipine in human intestinal and liver microsomes (HLM and HIM) was optimized yielding a Michaelis-Menten plot from where the K(m) and V(max) values were estimated by nonlinear regression. The flavonoids, naringin, naringenin, and quercetin, were subsequently incubated with felodipine at the determined K(m) value in HLM. Comparing results obtained from a known CYP3A4 inhibitor, verapamil, the flavonoids inhibited felodipine metabolism. In-depth computational analysis of these flavonoids in terms of CYP3A4 binding, sequencing, and affinity, computational biomimetism was employed to validate the potential CYP3A4 inhibitors. The modeled compounds were comparatively evaluated by incubation with felodipine in both HLM and HIM. Results showed that the polymers 8-arm-PEG, o-(2-aminoethyl)-o-methyl-PEG, 4-arm-PEG (molecular weight = 10,000 g/mol and 20,000 g/mol, respectively), and poly(l-lysine) were able to inhibit the felodipine metabolism with the half maximal inhibitory concentration (IC(50)) values ranging from 7.22 to 30.0 µM (HLM) and 5.78 to 41.03 µM (HIM). Molecular docking confirmed drug-enzyme interactions by computing the free energies of binding (ΔE) and inhibition constants (K(i)) of the docked compounds utilizing a Lamarckian Genetic Algorithm. Comparative correlations between the computed and experimental K(i) values were obtained. Computational modeling of CYP3A4 inhibitors provided a suitable strategy to screen pharmaceutical grade compounds that may potentially inhibit presystemic CYP3A4-dependent drug metabolism with the prospect of improving oral drug bioavailability.

Composite polylactic-methacrylic Acid copolymer nanoparticles for the delivery of methotrexate.

The purpose of this study was to develop poly(lactic acid)-methacrylic acid copolymeric nanoparticles with the potential to serve as nanocarrier systems for methotrexate (MTX) used in the chemotherapy of primary central nervous system lymphoma (PCNSL). Nanoparticles were prepared by a double emulsion solvent evaporation technique employing a 3-Factor Box-Behnken experimental design strategy. Analysis of particle size, absolute zeta potential, polydispersity (Pdl), morphology, drug-loading capacity (DLC), structural transitions through FTIR spectroscopy, and drug release kinetics was undertaken. Molecular modelling elucidated the mechanisms of the experimental findings. Nanoparticles with particle sizes ranging from 211.0 to 378.3 nm and a recovery range of 36.8-86.2 mg (Pdl ≤ 0.5) were synthesized. DLC values were initially low (12 ± 0.5%) but were finally optimized to 98 ± 0.3%. FTIR studies elucidated the comixing of MTX within the nanoparticles. An initial burst release (50% of MTX released in 24 hours) was obtained which was followed by a prolonged release phase of MTX over 84 hours. SEM images revealed near-spherical nanoparticles, while TEM micrographs revealed the presence of MTX within the nanoparticles. Stable nanoparticles were formed as corroborated by the chemometric modelling studies undertaken.

Surface-engineered nanoliposomes by chelating ligands for modulating the neurotoxicity associated with ß-amyloid aggregates of Alzheimer's disease.

PURPOSE: To develop chelating ligand-bound nanoliposomes (NLPs) for the prevention and reversal of ß-Amyloid (Aß) aggregation associated with promoting neurotoxicity in Alzheimer disease (AD). METHODS: Four different chelating ligands (CuAc, EDTA, histidine and ZnAc) were surface-engineered onto NLPs using either covalent or non-covalent conjugation. Successful conjugation of chelating ligands onto the surface of NLPs was confirmed by characterization studies: SEM, TEM and FTIR analysis. Chelation energetics of EDTA with Cu(II)/Zn(II)-Aß(10-21) and nanoformation of emulsified polymers were computed and corroborated with experimental and analytical data using chemometric molecular modeling. RESULTS: The modified NLPs produced were spherical in shape, 127-178 nm in size, with polydispersity index from 0.217-0.920 and zeta potential range of -9.59 to -37.3 mV. Conjugation efficiencies were 30-76 %, which confirmed that chelating ligands were attached to the NLP surface. CONCLUSIONS: In vitro and ex vivo results elucidated the effectiveness of chelating ligand-bound NLPs for prevention of CuAß(1-42) or ZnAß(1-42) aggregate buildup associated with neurotoxicity in PC12 neuronal cells, as well as promotion of intracellular uptake in the presence of Cu(II) or Zn(II) metal ions.

Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success.

The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal microenvironmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties. Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus-target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately.

The application of a crosslinked pectin-based wafer matrix for gradual buccal drug delivery.

The purpose of this study was to develop crosslinked wafer matrices and establish the influence of the crosslinker type and processing sequence on achieving gradual buccal drug delivery. Three sets of drug-loaded crosslinked pectin wafers were produced employing the model water-soluble antihistamine, diphenhydramine and were compared with noncrosslinked wafers. The formulations were crosslinked with CaCl(2), BaCl(2), or ZnSO(4) pre- or postlyophilization (sets 1 and 2) as well as pre- and postlyophilization (set 3), respectively. The surface morphology, porositometry, molecular vibrational transitions, textural attributes, thermal and in vitro drug release were characterized and supported by in silico molecular mechanics simulations. Results revealed that crosslinked wafers produced smaller pore sizes (107.63 Å) compared with noncrosslinked matrices (180.53 Å) due to molecular crosslinks formed between pectin chains. Drug release performance was dependent on the wafer crosslinking production sequence. Noncrosslinked wafers displayed burst-release with 82% drug released at t(30min) compared with first-order kinetic profiles obtained for prelyophilized crosslinked matrices (50% released at t(30min) followed by steady release). Wafers crosslinked postlyophilization displayed superior control of drug release (40% at t(30min)). Molecular mechanics simulations corroborated with the experimental data and established that Ba(++), having the largest atomic radii (1.35 Å) formed a number of ionic bridges producing wafers of higher porosity (0.048 cm(2)/g) and had more influence on drug release.

Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery.

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix(®) multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise(®), which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix(®) as well as "release modules assemblage", which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

Advanced preformulation investigations for the development of a lead intravaginal bioadhesive polymeric device.

CONTEXT AND OBJECTIVE: To screen various polymers through extensive preformulation investigations to ultimately obtain a lead polymer combination for designing a desirable Intravaginal Bioadhesive Polymeric Device (IBPD). MATERIALS AND METHODS: Hydrophilic and hydrophobic polymers (18) at different combinations were blended and compressed into 62 caplet-shaped devices at 5 tons, one of the hydrophilic polymers being a modified synthetic product of polyamide 6,10 ((m)PA 6,10). Two sets of crosslinked PAA-based caplets comprising either allyl-sucrose (AS-PAA) or allyl-penta-erythritol (APE-PAA) were explored. The devices were subjected to in-process validation tests and thereafter to preformulation investigational screening {equilibrium swelling ratio (ESR) being a screening parameter}, using a One Variable at a Time (OVAT) approach. Molecular mechanics force field simulations in both vacuum and solvated systems were conducted to investigate the influence of addition and subsequent replacement of a polymer(s) on the spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex, IBPD. RESULTS AND DISCUSSION: The developed devices were sufficiently strong (longitudinal crushing force:286 ± 0.01 N; mean weight:600 ± 0.48 mg; mean friability:0.31 ± 0.04%). Through OVAT approach, 15 lead formulations with minimal swelling tendencies (ESRs ranging from 0.011 to 0.084) were obtained out of 62 formulations. F62 {i.e. (m)PA 6,10, (150 mg), PLGA (400 mg), EC (200 mg), PVA (25 mg) and PAA (25 mg)} displayed minimal swelling tendency and therefore the highest stability. The highly stabilized conformation of the final in silico IBPD polymeric assembly PLGA-(m)PA6,10-PVA-PAA-EC corroborated the experimental results in terms of preformulation investigational screening using the OVAT approach. CONCLUSION: The results obtained suggest that (m)PA 6,10, PLGA, EC, PVA and PAA at an appropriate weight ratio may be suitable for development of an IBPD.