-
International Journal of Radiation... 2021Recent studies with doxycycline as adjuvant therapy to conventional chemotherapy have shown promising results in cancer therapy. The current study aimed to examine the...
PURPOSE
Recent studies with doxycycline as adjuvant therapy to conventional chemotherapy have shown promising results in cancer therapy. The current study aimed to examine the capability of Lu-labeled tetracycline ligand, doxycycline hyclate, to use as an anticancer agent.
MATERIALS AND METHODS
Doxycycline was radiolabeled with beta-emitting radioisotope Lu. Complex formation and its interaction with DNA were investigated electrochemically. Binding of Lu-doxycycline to CT 26 cell line was done. Biodistribution of Lu-doxycycline was examined in healthy Wistar rats and CT26 colon carcinoma tumor-bearing mice by i.v. and i.p. administration, respectively.
RESULTS
Doxycycline hyclate was successfully radiolabeled with Lu in high radiolabeling yield (>99%). The radiolabeled complex was stable in vitro in saline and human serum over 72 h. Non-radioactive Lu-doxycycline complex formation was demonstrated electrochemically as well. Intercalative interactions of the doxycycline and Lu-doxycycline with DNA were proved using simultaneously spectrophotometric and electrochemical methods. The binding of the radiolabeled complex with plasma proteins was 4.0 ± 0.4%. The partition coefficient showed the lipophilic nature of the complex similar to the free ligand. The binding curve demonstrates binding from 0.1 nM concentrations of Lu-doxycycline, with half-binding estimated ∼100 nM. Biodistribution studies of Lu-doxycycline in CT26 colon tumor-bearing mice showed a satisfactory accumulation rate in the tumor (2.88 ± 0.85% ID/g) 3 h after intraperitoneal injection. Both the hepatobiliary system and the urinary system were prominent as excretory routes of the radiolabeled complex.
CONCLUSION
Considering obtained results, Lu-doxycycline complex, due to its excellent electrochemical and biological characteristics, with emphasis on the binding ability to DNA intercalative interaction as well as significant accumulation in the tumor, is suitable for further in vivo studies to investigate its potential use in cancer treatment.
Topics: Animals; Cell Line, Tumor; Doxycycline; Ligands; Lutetium; Mice; Radiopharmaceuticals; Rats; Rats, Wistar; Tissue Distribution
PubMed: 34473599
DOI: 10.1080/09553002.2021.1976864 -
International Journal of Pharmaceutics Aug 2019Niosomes have been considered as promising nanoscale carriers for ocular drug delivery, since they have been shown to increase the bioavailability of various drugs and...
Niosomes have been considered as promising nanoscale carriers for ocular drug delivery, since they have been shown to increase the bioavailability of various drugs and to improve their efficacy. The main objective of this study was to prepare and characterize niosomes for ocular delivery of doxycycline hyclate. Niosomes were prepared using various surfactants (namely Span 20, Span 60, Span 80, Tween 60) and cholesterol in different molar ratios, using the thin film hydration method followed by multiple membrane extrusion or the reverse-phase evaporation method. In our hands highest entrapment efficiency was encountered with the formulation composed of Span 60 and cholesterol, prepared by the reverse phase evaporation method. Transmission electron microscopy and dynamic light scattering were used to assess the morphology, size and size distribution paterns of prepared niosomes. In vitro release studies showed sustained release of doxycycline from niosomes. After 2 months of storage at 4 °C the doxycycline-loaded niosomes remained physically stable in terms of encapsulation efficiency and particle size. The performed Draize test revealed that the prepared niosomes were well tolerated by the eye. Taken together our findings indicate that niosomes could be considered as a plausible drug delivery platform for for ophthalmic application of doxycycline.
Topics: Administration, Ophthalmic; Animals; Anti-Bacterial Agents; Doxycycline; Drug Delivery Systems; Drug Design; Eye; Liposomes; Male; Rabbits; Surface-Active Agents
PubMed: 31207279
DOI: 10.1016/j.ijpharm.2019.06.022 -
The American Journal of Digestive... Sep 1977Two patients developed acute esophageal ulceration after ingestion of doxycycline hyclate. Despite vigorous investigation no evidence was found to support a viral...
Two patients developed acute esophageal ulceration after ingestion of doxycycline hyclate. Despite vigorous investigation no evidence was found to support a viral etiology. The ulcers are postulated to result from close contact between the capsules and the esophageal mucosa.
Topics: Acute Disease; Adult; Doxycycline; Esophageal Diseases; Female; Humans; Male; Middle Aged; Peptic Ulcer
PubMed: 900095
DOI: 10.1007/BF01694511 -
Lancet (London, England) Nov 1982
Topics: Animals; Biotransformation; Doxycycline; Humans; Kidney; Liver; Mice; Rats
PubMed: 6128467
DOI: 10.1016/s0140-6736(82)92804-5 -
Journal of Pharmaceutical Sciences Dec 1975The bioavailability of three different brands and three different dosage forms of doxycycline was studied in normal subjects. Single doses, equivalent to 200 mg of...
The bioavailability of three different brands and three different dosage forms of doxycycline was studied in normal subjects. Single doses, equivalent to 200 mg of doxycycline, were administered to six subjects in a crossover design as the innovator's intravenous solution given orally (Treatment A), the innovator's capsule product (Treatment B), a noninnovator's capsule product (Treatment C), the innovator's oral suspension product (Treatment D), and a second noninnovator's capsule product (Treatment E). All dosage forms contained doxycycline as the hyclate, except the suspension which contained the nonhyclate form. Serum levels were determined periodically over 48 hr, and cumulative urinary excretion was measured concurrently over a 120-hr collection period. No statistically significant differences were observed in any in vivo indicator of bioequivalence when the three capsule products were compared. Consequently, they were judged to be bioequivalent. When these capsule products were compared to the oral solution, no statistically significant differences were observed. However, when the capsules and the suspension were compared, statistically significant differences were found in the rate of absorption. In vitro dissolution tests were also conducted on the three brands of capsules, and times required to achieve 50% dissolution showed rank-order correlation with corresponding absorption rate constants.
Topics: Adult; Biological Availability; Capsules; Doxycycline; Humans; Male; Solubility; Time Factors
PubMed: 1206500
DOI: 10.1002/jps.2600641229 -
American Journal of Veterinary Research Aug 2008To determine the pharmacokinetics after SC administration of an experimental, long-acting parenteral formulation of doxycycline hyclate in a poloxamer-based matrix and...
OBJECTIVE
To determine the pharmacokinetics after SC administration of an experimental, long-acting parenteral formulation of doxycycline hyclate in a poloxamer-based matrix and after IV and IM administration of an aqueous formulation of doxycycline hyclate in goats.
ANIMALS
30 clinically normal adult goats.
PROCEDURES
Goats were allocated to 3 groups (10 goats/group). One group of goats received doxycycline hyclate (10 mg/kg) IM, a second group received the same dosage of doxycycline hyclate IV, and the third group received the long-acting parenteral formulation of doxycycline hyclate SC. Serum concentrations of doxycycline were determined before and at various intervals after administration.
RESULTS
The long-acting parenteral formulation of doxycycline hyclate had the greatest bioavailability (545%); mean +/- SD maximum serum concentration was 2.4 +/- 0.95 microg/mL, peak time to maximum concentration was 19.23 +/- 2.03 hours, and elimination half-life was 40.92 +/- 4.25 hours.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that the long-acting parenteral formulation of doxycycline hyclate distributed quickly and widely throughout the body after a single dose administered SC, and there was a prolonged half-life. Bioavailability of the longacting parenteral formulation of doxycycline hyclate after SC administration was excellent, compared with bioavailability after IV and IM administration of an aqueous formulation of doxycycline hyclate. Although no local tissue irritation and adverse effects were detected, clinical assessment of drug-residues and toxicologic evaluations are warranted before this long-acting parenteral formulation of doxycycline hyclate can be considered for use in goats with bacterial infections.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Biological Availability; Doxycycline; Goat Diseases; Goats; Half-Life; Infusions, Parenteral; Injections
PubMed: 18672975
DOI: 10.2460/ajvr.69.8.1085 -
International Journal of Pharmaceutics Aug 2015The aim of the study was to evaluate kinetics of doxycycline hyclate release from polymeric bioresorbable implants and to examine suitability of this system for local...
The aim of the study was to evaluate kinetics of doxycycline hyclate release from polymeric bioresorbable implants and to examine suitability of this system for local treatment of periodontitis. Selected trimethylene carbonate/ϵ-caprolactone (TMC/CL) and glycolide/caprolactone (GL/CL) copolymers were synthesized and used as carriers in the form of small elastic rings with 5 wt% and 10 wt% doxycycline hyclate content, or in the form of flakes obtained through electro-spinning technique. The release of the drug under in vitro conditions has been tested. The study has shown that equimolar TMC/CL copolymer loaded with 10 wt% of doxycycline hyclate appears to be the most suitable copolymer for assumed system. The drug release proceeds mainly by diffusion of medium into the polymeric matrix and then the drug is washed out. Daily validation of doxycycline doses released by the system should ensure accurate course of the therapy.
Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Caproates; Delayed-Action Preparations; Dioxanes; Doxycycline; Drug Carriers; Drug Delivery Systems; Drug Design; Drug Implants; Lactones; Molecular Weight; Periodontitis; Water
PubMed: 26143233
DOI: 10.1016/j.ijpharm.2015.06.034 -
Acta Clinica Belgica 1992The hepatotoxicity of tetracyclines is well known. If microvesicular steatosis due to a high dose of tetracycline has virtually disappeared, it can also be observed with...
The hepatotoxicity of tetracyclines is well known. If microvesicular steatosis due to a high dose of tetracycline has virtually disappeared, it can also be observed with other drugs belonging to the tetracycline family. To our knowledge, hepatotoxicity induced by doxycycline has never been reported. In our patient, the abrupt onset of hepatic failure, five days after the start of doxycycline and the rapid normalization after the drug was stopped, leads to suspect a causal relationship between doxycycline and liver insufficiency. We must however be careful before concluding, because our patient received also acetylsalicylic acid and paracetamol, two other potential hepatotoxic drugs.
Topics: Adult; Chemical and Drug Induced Liver Injury; Doxycycline; Female; Humans; Liver; Periapical Abscess
PubMed: 1332350
DOI: 10.1080/17843286.1992.11718230 -
Archives of Internal Medicine Jul 1997Although several new antibiotics have recently become available, in several clinical instances conventional antibiotics may be equally efficacious at a considerably... (Review)
Review
Although several new antibiotics have recently become available, in several clinical instances conventional antibiotics may be equally efficacious at a considerably lower cost. In today's era of cost containment, it is particularly relevant to revisit older, inexpensive antibiotics to reexplore their role in the face of the emergence of resistant microorganisms and competition from newer agents. Doxycycline is one such antibiotic. It is an inexpensive, broad-spectrum antimicrobial agent that remains the drug of first choice for several infections. In addition, it can be used for a variety of other indications. Adverse effects are infrequent and relatively minor. While interactions occur with several medications, none of these interactions has significant adverse consequences.
Topics: Animals; Anti-Bacterial Agents; Doxycycline; Drug Interactions; Humans
PubMed: 9224219
DOI: No ID Found -
Veterinary and Human Toxicology Oct 1988Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966. The molecule, obtained semi-synthetically from oxytetracycline or... (Review)
Review
Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966. The molecule, obtained semi-synthetically from oxytetracycline or methacycline, is highly lipophilic permitting excellent penetration into tissues. In vitro antimicrobial activity of doxycycline is superior to that of the older tetracyclines (chlortetracycline, oxytetracycline, tetracycline). In laboratory animals, the protective dose for 50% of the subjects (PD50) demonstrates a better in vivo activity than that of all other members of the tetracycline family. Clinical use in human medicine has confirmed the efficacy of doxycycline for a variety of infectious conditions. High lipophilicity results in a large volume of distribution, substantial binding to plasma proteins, and reabsorption in the renal tubules and gastrointestinal tract, thereby conferring a long elimination half-life to the drug. Excellent absorption after oral administration allows small oral doses and minimizes the known side effects of tetracyclines on the gastrointestinal tract--irritation and suprainfection. The contrast to the other tetracyclines, doxycycline does not accumulate in renal failure due to a compensatory gastrointestinal secretion. The pharmacology, toxicology and therapeutics of doxycycline in laboratory animals and man indicate that this drug may be a valuable antimicrobial for use in veterinary medicine.
Topics: Animals; Chemical Phenomena; Chemistry; Doxycycline; Humans
PubMed: 3055652
DOI: No ID Found