title: Novel biopolymers as implant matrix for the delivery of ciprofloxacin: biocompatibility, degradation, and in vitro antibiotic release.
abstract: The purpose of this study was to investigate the in vitro-in vivo degradation and tissue compatibility of three novel biopolymers viz. polymerized rosin (PR), glycerol ester of polymerized rosin (GPR) and pentaerythritol ester of polymerized rosin (PPR) and study their potential as implant matrix for the delivery of ciprofloxacin hydrochloride. Free films of polymers were used for in vitro degradation in PBS (pH 7.4) and in vivo in rat subcutaneous model. Sample weight loss, molecular weight decline, and morphological changes were analyzed after periodic intervals (30, 60, and 90 days) to monitor the degradation profile. Biocompatibility was evaluated by examination of the inflammatory tissue response to the implanted films on postoperative days 7, 14, 21, and 28. Furthermore, direct compression of dry blends of various polymer matrices with 20%, 30%, and 40% w/w drug loading was performed to investigate their potential for implant systems. The implants were characterized in terms of porosity and ciprofloxacin release. Biopolymer films showed slow rate of degradation, in vivo rate being faster on comparative basis. Heterogeneous bulk degradation was evident with the esterified products showing faster rates than PR. Morphologically all the films were stiff and intact with no significant difference in their appearance. The percent weight remaining in vivo was 90.70 +/- 6.2, 85.59 +/- 5.8, and 75.56 +/- 4.8 for PR, GPR, and PPR films respectively. Initial rapid drop in Mw was demonstrated with nearly 20.0% and 30.0% decline within 30 days followed by a steady decline to nearly 40.0% and 50.0% within 90 days following in vitro and in vivo degradation respectively. Biocompatibility demonstrated by acute and subacute tissue reactions showed minimal inflammatory reactions with prominent fibrous encapsulation and absence of necrosis demonstrating good tissue compatibility to the extent evaluated. All implants showed erosion and increase in porosity that affected the drug release. Increase in drug loading significantly altered the ciprofloxacin release in extended dissolution studies. PPR produced drug release >90% over a period of 90 days promising its utility in implant systems. The results demonstrated the utility of novel film forming biopolymers as implant matrix for controlled/sustained drug delivery with excellent biocompatibility characteristics.
authors.affiliation: Department of Pharmaceutical Sciences, Nagpur University Campus, Amravati Road, Nagpur-440 033, India.
authors.forename: Suniket V
authors.initials: SV
authors.lastname: Fulzele
authors.forename: Prashant M
authors.initials: PM
authors.lastname: Satturwar
authors.forename: Avinash K
authors.initials: AK
authors.lastname: Dorle
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001704:Biopolymers / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D001711:Biotransformation; D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005549:Foreign-Body Reaction / Q000139:chemically induced / Q000473:pathology; D005989:Glycerides / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D016062:Porosity; D011409:Propylene Glycols / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012116:Resins, Plant / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D040521:Subcutaneous Tissue / Q000473:pathology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001704:Biopolymers; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005989:Glycerides; D011409:Propylene Glycols; D012116:Resins, Plant; C514097:glyceryl-hydrogenated rosinate; D002939:Ciprofloxacin; C013893:rosin; C487451:pentaerythritol rosinate